Trial Outcomes & Findings for A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies (NCT NCT03088878)
NCT ID: NCT03088878
Last Updated: 2025-02-12
Results Overview
Defined as achievement of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL, per standardized criteria \[Hallek 2008\], as recently updated \[Hallek 2018; Cheson 2012\]; and the achievement of a CR or PR for those with MCL or MZL, per based on standardized criteria \[Cheson 2007\] as recently updated \[Cheson 2014\].
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
95 participants
Primary outcome timeframe
up to 5 years
Results posted on
2025-02-12
Participant Flow
Participant milestones
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
3
|
21
|
3
|
3
|
3
|
3
|
3
|
3
|
16
|
18
|
10
|
|
Overall Study
Efficacy Population CLL (Parts 1 & 2)
|
0
|
0
|
0
|
0
|
0
|
3
|
3
|
3
|
3
|
3
|
3
|
16
|
0
|
0
|
|
Overall Study
Efficacy Population (Part 3)
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
16
|
7
|
|
Overall Study
Efficacy Population MCL (Parts 1 & 2)
|
3
|
3
|
3
|
3
|
16
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
3
|
3
|
21
|
3
|
3
|
3
|
3
|
3
|
3
|
16
|
18
|
10
|
Reasons for withdrawal
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
4
|
2
|
1
|
0
|
0
|
0
|
0
|
0
|
5
|
3
|
|
Overall Study
Clinical Progression
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Disease Progression
|
1
|
2
|
3
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Overall Study
Initiation of Alternative Treatment
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
4
|
1
|
1
|
0
|
1
|
2
|
0
|
2
|
1
|
0
|
|
Overall Study
Terminated by Sponsor
|
2
|
1
|
0
|
1
|
6
|
0
|
0
|
0
|
0
|
0
|
3
|
13
|
2
|
1
|
|
Overall Study
Completed 2 years of Treatment
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
8
|
3
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
COVID Related noncompliance
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Drug or Study Noncompliance
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies
Baseline characteristics by cohort
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=21 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600 mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=18 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=10 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
Total
n=95 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
66.3 years
STANDARD_DEVIATION 2.1 • n=5 Participants
|
63.7 years
STANDARD_DEVIATION 6.0 • n=7 Participants
|
59.0 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
56.7 years
STANDARD_DEVIATION 11.6 • n=4 Participants
|
66.6 years
STANDARD_DEVIATION 9.3 • n=21 Participants
|
62.3 years
STANDARD_DEVIATION 7.6 • n=8 Participants
|
74.0 years
STANDARD_DEVIATION 13.1 • n=8 Participants
|
71.3 years
STANDARD_DEVIATION 8.1 • n=24 Participants
|
68.7 years
STANDARD_DEVIATION 9.0 • n=42 Participants
|
74.0 years
STANDARD_DEVIATION 2.7 • n=42 Participants
|
71.3 years
STANDARD_DEVIATION 4.9 • n=42 Participants
|
64.3 years
STANDARD_DEVIATION 9.5 • n=42 Participants
|
66.2 years
STANDARD_DEVIATION 9.2 • n=36 Participants
|
64.7 years
STANDARD_DEVIATION 6.7 • n=36 Participants
|
66.0 years
STANDARD_DEVIATION 8.9 • n=24 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
8 Participants
n=36 Participants
|
7 Participants
n=36 Participants
|
29 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=24 Participants
|
3 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
12 Participants
n=42 Participants
|
10 Participants
n=36 Participants
|
3 Participants
n=36 Participants
|
66 Participants
n=24 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
3 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
1 Participants
n=36 Participants
|
4 Participants
n=24 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
3 Participants
n=24 Participants
|
3 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
15 Participants
n=42 Participants
|
15 Participants
n=36 Participants
|
8 Participants
n=36 Participants
|
78 Participants
n=24 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=36 Participants
|
7 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=24 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
21 participants
n=21 Participants
|
3 participants
n=8 Participants
|
3 participants
n=8 Participants
|
3 participants
n=24 Participants
|
3 participants
n=42 Participants
|
3 participants
n=42 Participants
|
3 participants
n=42 Participants
|
16 participants
n=42 Participants
|
18 participants
n=36 Participants
|
10 participants
n=36 Participants
|
95 participants
n=24 Participants
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.
Defined as achievement of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL, per standardized criteria \[Hallek 2008\], as recently updated \[Hallek 2018; Cheson 2012\]; and the achievement of a CR or PR for those with MCL or MZL, per based on standardized criteria \[Cheson 2007\] as recently updated \[Cheson 2014\].
Outcome measures
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=16 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=7 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Response
|
3 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
14 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
15 Participants
|
15 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.
Defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using Kaplan-Meier Survival Methods.
Outcome measures
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=16 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=7 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression Free Survival (PFS)
|
NA months
Interval 35.9 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
Interval 16.5 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
4.3 months
Interval 0.03 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
36.3 months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
Interval 15.7 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
Interval 41.6 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
Interval 25.9 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
NA months
Interval 11.0 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI.
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.
Defined as the interval from the start of study therapy to death from any cause. Overall Survival was analyzed using Kaplan-Meier Survival methods.
Outcome measures
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
n=16 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=16 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=7 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 18.8 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
22.5 months
Interval 11.5 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 14.0 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 36.3 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 15.7 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 41.6 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 19.7 to
NA for median indicates that there were not enough OS events (i.e., death) to estimate the median time to OS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The subset of the efficacy population achieving Objective Response (ORR). The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.
Defined as the amount of time (months) for achieving of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL; and the amount of time (months) for achieving of a CR or PR for those with MCL.
Outcome measures
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=2 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=14 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=2 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=2 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
n=15 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=15 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=7 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response
|
NA months
Interval 34.1 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 13.8 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
11.9 months
Interval 1.5 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
33.5 months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
38.8 months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
40.3 months
Interval 19.6 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 22.2 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
Interval 8.3 to
NA for median indicates that there were not enough Duration of Response events (i.e., progressive disease or death) to estimate the median time to Duration of Response (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: A subset of the efficacy population with a positive Del(17p) mutation. The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.
Defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause, in patients with TP53 mutation status
Outcome measures
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=1 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=1 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=5 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=1 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600mg
n=6 Participants
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=3 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=1 Participants
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-free Survival (PFS) for Patients With TP53 Mutation Status
|
—
|
16.5 months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
17.3 months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
—
|
NA months
Interval 2.8 to
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
—
|
—
|
—
|
—
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
—
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
NA months
NA for median indicates that there were not enough PFS events (i.e., progressive disease or death) to estimate the median time to PFS (i.e. 50% Survival). NA for the 95% CI limits indicates that there were not enough events above/below the 50% survival proportion to estimate the limit of the CI. Kaplan-Meier Survival methods were used for reporting analysis results.
|
Adverse Events
MCL Phase 1b, Part 1: 2mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
MCL Phase 1b, Part 1: 4mg/kg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
MCL Phase 1b, Part 1: 8mg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 3 deaths
MCL Phase 1b, Part 1: 16 mg/kg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
MCL Phase 1b, Part 2: 600 mg
Serious events: 13 serious events
Other events: 21 other events
Deaths: 7 deaths
CLL Phase 1b, Part 1: 2 mg/kg
Serious events: 3 serious events
Other events: 3 other events
Deaths: 1 deaths
CLL Phase 1b, Part 1: 4 mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
CLL Phase 1b, Part 1: 8 mg/kg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
CLL Phase 1b, Part 1: 16 mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
CLL Phase 1b, Part 1: 300 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
CLL Phase 1b, Part 1: 600 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
CLL Phase 1b, Part 2: 600 mg
Serious events: 5 serious events
Other events: 15 other events
Deaths: 1 deaths
CLL Phase 2, Part 3: 600 mg
Serious events: 9 serious events
Other events: 18 other events
Deaths: 3 deaths
CLL Phase 2, Part 3: Ibrutinib Alone
Serious events: 5 serious events
Other events: 9 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=21 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600 mg
n=16 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=18 participants at risk
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=10 participants at risk
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
General disorders
Pyrexia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Acute Sinusitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Adenocarcinoma
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Metabolism and nutrition disorders
Tumor Lysis Syndrome
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
9.5%
2/21 • Number of events 2 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
11.1%
2/18 • Number of events 2 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 2 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Campylobacter Gastroenteritis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Cellulitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 2 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Cellulitis Staphylococcal
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Corona Virus Infection
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Erosive Oesophagitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypnonatraemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
General disorders
Odema Peripheral
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Pericardial Effusion
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
9.5%
2/21 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
11.1%
2/18 • Number of events 2 • Up to 5 years
|
20.0%
2/10 • Number of events 2 • Up to 5 years
|
|
Cardiac disorders
Respiratory Failure
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Staphylococcal Infection
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid Cancer Metastatic
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Ear and labyrinth disorders
Vestibular Disorder
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Cardiac Tamponade
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Cardiac disorders
Pericardial Haemorrhage
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Investigations
Coronavirus Test Positive
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine Tumour
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Renal and urinary disorders
Urinary Retention
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Vascular disorders
Atheroembolism
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
General disorders
Asthenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Infections and infestations
Eschericha Urinary Tract Infection
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Vascular disorders
Hypertensive Crisis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Blood and lymphatic system disorders
Autoimmune Haemolytic Anaemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Pseudohyperkalaemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/21 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
0.00%
0/18 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
Other adverse events
| Measure |
MCL Phase 1b, Part 1: 2mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 4mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 8mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 1: 16 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
MCL Phase 1b, Part 2: 600 mg
n=21 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 2 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 4 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 8 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 16 mg/kg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 300 mg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 1: 600 mg
n=3 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 1b, Part 2: 600 mg
n=16 participants at risk
Part 1:
* Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL.
* Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL).
Part 2:
* Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV).
* Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
|
CLL Phase 2, Part 3: 600 mg
n=18 participants at risk
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
CLL Phase 2, Part 3: Ibrutinib Alone
n=10 participants at risk
Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list:
* Arm A: cirmtuzumab + ibrutinib
* Arm B: ibrutinib alone
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
66.7%
2/3 • Number of events 3 • Up to 5 years
|
28.6%
6/21 • Number of events 8 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
18.8%
3/16 • Number of events 3 • Up to 5 years
|
16.7%
3/18 • Number of events 6 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
9.5%
2/21 • Number of events 2 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
12.5%
2/16 • Number of events 2 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • Up to 5 years
|
100.0%
3/3 • Number of events 3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
14.3%
3/21 • Number of events 4 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
25.0%
4/16 • Number of events 5 • Up to 5 years
|
27.8%
5/18 • Number of events 6 • Up to 5 years
|
0.00%
0/10 • Up to 5 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
4.8%
1/21 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
12.5%
2/16 • Number of events 4 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
4.8%
1/21 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
5.6%
1/18 • Number of events 1 • Up to 5 years
|
10.0%
1/10 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
19.0%
4/21 • Number of events 6 • Up to 5 years
|
66.7%
2/3 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
6.2%
1/16 • Number of events 1 • Up to 5 years
|
11.1%
2/18 • Number of events 2 • Up to 5 years
|
30.0%
3/10 • Number of events 4 • Up to 5 years
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
3/3 • Number of events 7 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
100.0%
3/3 • Number of events 5 • Up to 5 years
|
100.0%
3/3 • Number of events 6 • Up to 5 years
|
42.9%
9/21 • Number of events 14 • Up to 5 years
|
33.3%
1/3 • Number of events 5 • Up to 5 years
|
66.7%
2/3 • Number of events 3 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
50.0%
8/16 • Number of events 16 • Up to 5 years
|
27.8%
5/18 • Number of events 7 • Up to 5 years
|
50.0%
5/10 • Number of events 8 • Up to 5 years
|
|
General disorders
Fatigue
|
100.0%
3/3 • Number of events 7 • Up to 5 years
|
100.0%
3/3 • Number of events 4 • Up to 5 years
|
66.7%
2/3 • Number of events 2 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
7/21 • Number of events 7 • Up to 5 years
|
66.7%
2/3 • Number of events 4 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
66.7%
2/3 • Number of events 3 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 1 • Up to 5 years
|
33.3%
1/3 • Number of events 2 • Up to 5 years
|
43.8%
7/16 • Number of events 9 • Up to 5 years
|
33.3%
6/18 • Number of events 12 • Up to 5 years
|
40.0%
4/10 • Number of events 6 • Up to 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place