Trial Outcomes & Findings for Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (NCT NCT02446236)
NCT ID: NCT02446236
Last Updated: 2025-01-30
Results Overview
Define maximum tolerated dose (MTD) and /or recommended phase II dose for the combinations of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) plus lenalidomide / rituximab in relapsed or refractory MCL by assessing the incidence of dose limiting toxicities (DLTs) in cycle 1 through an assessment of adverse events
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
28 Days
Results posted on
2025-01-30
Participant Flow
Participant milestones
| Measure |
Phase I - Dose Level 1
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 15mg PO days 1-21
|
Phase I - Dose Level 2
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Phase II Expansion
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
3
|
19
|
|
Overall Study
COMPLETED
|
4
|
3
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
2
|
Reasons for withdrawal
| Measure |
Phase I - Dose Level 1
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 15mg PO days 1-21
|
Phase I - Dose Level 2
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Phase II Expansion
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
|---|---|---|---|
|
Overall Study
Screen Failure
|
1
|
0
|
1
|
|
Overall Study
Actively Receiving Therapy
|
0
|
0
|
1
|
Baseline Characteristics
Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
Phase I - Dose Level 1
n=4 Participants
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 15mg PO days 1-21
|
Phase I - Dose Level 2
n=3 Participants
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Phase II Expansion
n=18 Participants
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Age, Continuous
|
69.5 Years
n=5 Participants
|
71 Years
n=7 Participants
|
65.5 Years
n=5 Participants
|
67 Years
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Ethnicity (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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
|
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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
18 participants
n=5 Participants
|
25 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 28 DaysPopulation: Phase I Cohorts
Define maximum tolerated dose (MTD) and /or recommended phase II dose for the combinations of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) plus lenalidomide / rituximab in relapsed or refractory MCL by assessing the incidence of dose limiting toxicities (DLTs) in cycle 1 through an assessment of adverse events
Outcome measures
| Measure |
Dose Escalation Study
n=7 Participants
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 10-25 mg PO days 1-21
Lenalidomide: Dose escalation of lenalidomide. Patients will receive 10, 15, 20, or 25 mg PO days 1-21
Ibrutinib: 560 mg PO daily
Rituximab: 375 mg/m2 IV Day 1
|
|---|---|
|
Determine the MTD (Measured in mg) Based on the Number of Patients With Adverse Events
|
20 mg
|
SECONDARY outcome
Timeframe: Through 28 Days After Discontinuation of Study DrugAssess safety and tolerability of the combinations through the review of adverse events. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off studyAssess preliminary anti-tumor activity of the combinations by radiological progression-free survival. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off studyAssess preliminary anti-tumor activity of the combinations by radiological response rate. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through 28 Days After Discontinuation of Study DrugInvestigate potential drug-drug interaction between Ibrutinib (PCI-32765) plus lenalidomide / rituximab. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Outcome measures
Outcome data not reported
Adverse Events
Phase I - Dose Level 1
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Phase I - Dose Level 2
Serious events: 2 serious events
Other events: 2 other events
Deaths: 2 deaths
Phase II Expansion
Serious events: 11 serious events
Other events: 10 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Phase I - Dose Level 1
n=4 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 15mg PO days 1-21
|
Phase I - Dose Level 2
n=3 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Phase II Expansion
n=18 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
|---|---|---|---|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/18
|
|
Cardiac disorders
Cardiogenic Shock
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4
|
0.00%
0/3
|
11.1%
2/18 • Number of events 2
|
|
Investigations
Fever
|
0.00%
0/4
|
0.00%
0/3
|
16.7%
3/18 • Number of events 3
|
|
Gastrointestinal disorders
GI Bleed
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/18
|
|
Nervous system disorders
Guillain-Barre Syndrome
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Influenza
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Eye disorders
Preseptal Orbital Cellulitis
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Psychiatric disorders
Psychiatric Decompensation
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy
|
0.00%
0/4
|
0.00%
0/3
|
11.1%
2/18 • Number of events 2
|
|
Infections and infestations
Sepsis
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Septic Sacrolitiis and Osteomyelitis with Numerous Abscesses
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/4
|
0.00%
0/3
|
11.1%
2/18 • Number of events 2
|
|
Infections and infestations
Upper Respiratory Infection
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/18
|
Other adverse events
| Measure |
Phase I - Dose Level 1
n=4 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 15mg PO days 1-21
|
Phase I - Dose Level 2
n=3 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
Phase II Expansion
n=18 participants at risk
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 20 mg PO days 1-21
|
|---|---|---|---|
|
Cardiac disorders
Arrythmia
|
0.00%
0/4
|
0.00%
0/3
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4
|
0.00%
0/3
|
16.7%
3/18 • Number of events 3
|
|
Infections and infestations
Infection
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/4
|
0.00%
0/3
|
11.1%
2/18 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
16.7%
3/18 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
27.8%
5/18 • Number of events 5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place