Phase 1b Safety and Efficacy Study of TRU-016

NCT ID: NCT01644253

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2021-04-21

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of TRU-016 in combination with rituximab, in combination with obinutuzumab, in combination with rituximab and idelalisib, or in combination with ibrutinib in patients with CLL; and in combination with bendamustine in patients with PTCL.

Detailed Description

The study will consist of 8 dose cohorts:

1. Previously untreated patients 20 mg/kg TRU-016 + rituximab.

2. Relapsed patients, 20 mg/kg TRU-016 + rituximab.

3. Previously untreated patients 10 mg/kg TRU-016 + rituximab.

4. Previously untreated patients TRU-016 + obinutuzumab.

5. Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib.

6. Patients with CLL on ibrutinib or another BTK inhibitor for a total of more than 1 year who have not had a complete response (CR) will continue receiving ibrutinib or another BTK inhibitor.

7. Patients with CLL on ibrutinib or another BTK inhibitor with stable disease and in whom the cysteine 481 mutant clone is present at a level >1%, will continue receiving ibrutinib or the alternative BTK inhibitor.

8. Patients with relapsed or refractory PTCL will receive TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days) + bendamustine for 2 days every cycle for 6 cycles.

Conditions

Chronic Lymphocytic Leukemia; Peripheral T-cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - Previously Untreated CLL

20 mg/kg TRU-016 + Rituximab

Group Type: EXPERIMENTAL

20 mg/kg TRU-016 + Rituximab

Intervention Type: BIOLOGICAL

TRU-016: 10 mg/kg for first dose, all subsequent doses 20 mg/kg, IV once weekly for 8 weeks followed by 4 monthly doses

Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV once weekly for 8 weeks followed by 4 monthly doses

Cohort 2 - Relapsed CLL

20 mg/kg TRU-016 + Rituximab

Group Type: EXPERIMENTAL

20 mg/kg TRU-016 + Rituximab

Intervention Type: BIOLOGICAL

TRU-016: 10 mg/kg for first dose, all subsequent doses 20 mg/kg, IV once weekly for 8 weeks followed by 4 monthly doses

Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV once weekly for 8 weeks followed by 4 monthly doses

Cohort 3 - Previously Untreated CLL

10 mg/kg TRU-016 + Rituximab

Group Type: EXPERIMENTAL

10 mg/kg TRU-016 + Rituximab

Intervention Type: BIOLOGICAL

TRU-016: 6 mg/kg for first dose, all subsequent doses 10 mg/kg, IV on Day 1, 8 and 15, followed by 5 monthly doses

Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV following TRU-016 schedule

Cohort 4 - Previously Untreated CLL

20 mg/kg TRU-016 20 + Obinutuzumab

Group Type: EXPERIMENTAL

TRU-016 20 mg/kg + Obinutuzumab

Intervention Type: BIOLOGICAL

TRU-016: 6 mg/kg on Day 1, 20 mg/kg on Day 8 and 15, then 20 mg/kg once a month for 5 months

Obinutuzumab: 100 mg on Day 1, 900 mg on Day 2, 1,000 mg on Day 8 and 15, then 1,000 mg once a month for 5 months

Cohort 5 - Relapse CLL

20 mg/kg TRU-016 + idelalisib + rituximab

Group Type: EXPERIMENTAL

TRU-016 6-20 mg/kg + idelalisib + rituximab

Intervention Type: BIOLOGICAL

TRU-016: 6 mg/kg on Days 15-36 weekly, 10 mg/kg on Days 43 and 50, then 20 mg/kg once a month for 5 months.

Cohort 6 - With CLL on ibrutinib with no complete response

20 mg/kg TRU-016 + ibrutinib

Group Type: EXPERIMENTAL

TRU-016 10-20 mg/kg + ibrutinib

Intervention Type: BIOLOGICAL

TRU-016: Dosed weekly for 8 weeks followed by 4 monthly intravenous (IV) infusions. The first dose will be 10 mg/kg and all subsequent doses will be 20 mg/kg.

Cohort 7 - With CLL on ibrutinib with stable disease

20 mg/kg TRU-016 + ibrutinib

Group Type: EXPERIMENTAL

TRU-016 10-20 mg/kg + ibrutinib

Intervention Type: BIOLOGICAL

TRU-016: Dosed weekly for 8 weeks followed by 4 monthly intravenous (IV) infusions. The first dose will be 10 mg/kg and all subsequent doses will be 20 mg/kg.

Cohort 8 - With relapsed or refractory PTCL

20 mg/kg TRU-016 + 90 mg/m2 bendamustine

Group Type: EXPERIMENTAL

TRU-016 10-20 mg/kg + bendamustine

Intervention Type: BIOLOGICAL

TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days). Bendamustine (90 mg/m2 on days 2 and 3 of cycle 1 and then days 1 and 2 of cycles 2 to 6) will be infused after completion of TRU-016. If a patient is benefiting with stable disease or better, then TRU-016 may continue to be dosed every 3 weeks after the first 6 cycles; bendamustine will not be dosed beyond 6 cycles.

Interventions

20 mg/kg TRU-016 + Rituximab

TRU-016: 10 mg/kg for first dose, all subsequent doses 20 mg/kg, IV once weekly for 8 weeks followed by 4 monthly doses

Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV once weekly for 8 weeks followed by 4 monthly doses

Intervention Type: BIOLOGICAL

10 mg/kg TRU-016 + Rituximab

TRU-016: 6 mg/kg for first dose, all subsequent doses 10 mg/kg, IV on Day 1, 8 and 15, followed by 5 monthly doses

Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV following TRU-016 schedule

Intervention Type: BIOLOGICAL

TRU-016 20 mg/kg + Obinutuzumab

TRU-016: 6 mg/kg on Day 1, 20 mg/kg on Day 8 and 15, then 20 mg/kg once a month for 5 months

Obinutuzumab: 100 mg on Day 1, 900 mg on Day 2, 1,000 mg on Day 8 and 15, then 1,000 mg once a month for 5 months

Intervention Type: BIOLOGICAL

TRU-016 6-20 mg/kg + idelalisib + rituximab

TRU-016: 6 mg/kg on Days 15-36 weekly, 10 mg/kg on Days 43 and 50, then 20 mg/kg once a month for 5 months.

Intervention Type: BIOLOGICAL

TRU-016 10-20 mg/kg + ibrutinib

TRU-016: Dosed weekly for 8 weeks followed by 4 monthly intravenous (IV) infusions. The first dose will be 10 mg/kg and all subsequent doses will be 20 mg/kg.

Intervention Type: BIOLOGICAL

TRU-016 10-20 mg/kg + bendamustine

TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days). Bendamustine (90 mg/m2 on days 2 and 3 of cycle 1 and then days 1 and 2 of cycles 2 to 6) will be infused after completion of TRU-016. If a patient is benefiting with stable disease or better, then TRU-016 may continue to be dosed every 3 weeks after the first 6 cycles; bendamustine will not be dosed beyond 6 cycles.

Intervention Type: BIOLOGICAL

Other Intervention Names

Rituxan; Rituxan; Gazyva; Zydelig, Rituxan; Imbruvica

Eligibility Criteria

Inclusion Criteria

• Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL.
• No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of >1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies.
• At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months
• For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference
• Age >/= to 18 years
• ECOG performance status of </= 2
• Life expectancy > 6 months in opinion of Investigator
• Serum creatinine, total bilirubin, ALT/SGPT </= 2.0 x upper limit of normal
• ANC >/= 800/mm3, Cohort 8 (PTCL): ANC >/= 1000/mm3
• Platelets >/= 30,000/mm3

Exclusion Criteria

• For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment.
• Has received an investigational therapy within 30 days of first dose of study drug
• Previous or concurrent additional malignancy
• Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease
• Positive serology for HIV or hepatitis C
• Hepatitis B surface antigen or hepatitis B core antibody positive
• Pregnant or breastfeeding
• Known current drug or alcohol abuse

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aptevo Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott C. Stromatt, M.D.

Role: STUDY_DIRECTOR

Aptevo Therapeutics

Locations

Augusta, Georgia, United States

Columbus, Ohio, United States

Eastern Regional Medical Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Greenville Health System

Greenville, South Carolina, United States

Houston, Texas, United States

Swedish Cancer Institute,1221 Madison St.

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

16009

Identifier Type: -

Identifier Source: org_study_id