Phase 1b Safety and Efficacy Study of TRU-016
Status: | Active, not recruiting |
---|---|
Conditions: | Blood Cancer, Lymphoma |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 11/30/2018 |
Start Date: | September 2012 |
End Date: | December 2019 |
Phase 1b, Open Label Study to Evaluate Safety and Efficacy of TRU-016 in Combination With Rituximab, Obinutuzumab, Rituximab and Idelalisib, or Ibrutinib in Chronic Lymphocytic Leukemia and With Bendamustine in Peripheral T-cell Lymphoma
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.
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.
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.
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.
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
We found this trial at
5
sites
Greenville, South Carolina 29615
Principal Investigator: Elizabeth Cull, MD
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1221 Madison Street
Seattle, Washington 98104
Seattle, Washington 98104
Principal Investigator: Krish Patel, MD
Phone: 206-386-2444
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