Phase 1b Safety and Efficacy Study of TRU-016

Aptevo Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Chronic Lymphocytic Leukemia; Peripheral T-cell Lymphoma

Treatments: Biological: TRU-016 10-20 mg/kg + bendamustine; Biological: 20 mg/kg TRU-016 + Rituximab; Biological: 10 mg/kg TRU-016 + Rituximab; Biological: TRU-016 10-20 mg/kg + ibrutinib; Biological: TRU-016 20 mg/kg + Obinutuzumab; Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01644253

16009

Details and patient eligibility

About

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.

Full 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.

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

87 participants in 8 patient groups

Cohort 1 - Previously Untreated CLL

Experimental group

Description:

20 mg/kg TRU-016 + Rituximab

Treatment:

Biological: 20 mg/kg TRU-016 + Rituximab

Cohort 2 - Relapsed CLL

Experimental group

Description:

20 mg/kg TRU-016 + Rituximab

Treatment:

Biological: 20 mg/kg TRU-016 + Rituximab

Cohort 3 - Previously Untreated CLL

Experimental group

Description:

10 mg/kg TRU-016 + Rituximab

Treatment:

Biological: 10 mg/kg TRU-016 + Rituximab

Cohort 4 - Previously Untreated CLL

Experimental group

Description:

20 mg/kg TRU-016 20 + Obinutuzumab

Treatment:

Biological: TRU-016 20 mg/kg + Obinutuzumab

Cohort 5 - Relapse CLL

Experimental group

Description:

20 mg/kg TRU-016 + idelalisib + rituximab

Treatment:

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

Cohort 6 - With CLL on ibrutinib with no complete response

Experimental group

Description:

20 mg/kg TRU-016 + ibrutinib

Treatment:

Biological: TRU-016 10-20 mg/kg + ibrutinib

Cohort 7 - With CLL on ibrutinib with stable disease

Experimental group

Description:

20 mg/kg TRU-016 + ibrutinib

Treatment:

Biological: TRU-016 10-20 mg/kg + ibrutinib

Cohort 8 - With relapsed or refractory PTCL

Experimental group

Description:

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

Treatment:

Biological: TRU-016 10-20 mg/kg + bendamustine