- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01644253
Phase 1b Safety and Efficacy Study of TRU-016
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
Study Overview
Status
Detailed Description
The study will consist of 8 dose cohorts:
- Previously untreated patients 20 mg/kg TRU-016 + rituximab.
- Relapsed patients, 20 mg/kg TRU-016 + rituximab.
- Previously untreated patients 10 mg/kg TRU-016 + rituximab.
- Previously untreated patients TRU-016 + obinutuzumab.
- Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib.
- 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.
- 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.
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Georgia
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Augusta, Georgia, United States, 30912
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Ohio
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Columbus, Ohio, United States, 43210
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19124
- Eastern Regional Medical Center
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Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh
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South Carolina
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Greenville, South Carolina, United States, 29605
- Greenville Health System
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Texas
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Houston, Texas, United States, 77030
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
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Seattle, Washington, United States, 98104
- Swedish Cancer Institute,1221 Madison St.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort 1 - Previously Untreated CLL
20 mg/kg TRU-016 + Rituximab
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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
Other Names:
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Experimental: Cohort 2 - Relapsed CLL
20 mg/kg TRU-016 + Rituximab
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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
Other Names:
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Experimental: Cohort 3 - Previously Untreated CLL
10 mg/kg TRU-016 + Rituximab
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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
Other Names:
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Experimental: Cohort 4 - Previously Untreated CLL
20 mg/kg TRU-016 20 + Obinutuzumab
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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
Other Names:
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Experimental: Cohort 5 - Relapse CLL
20 mg/kg TRU-016 + idelalisib + rituximab
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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.
Other Names:
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Experimental: Cohort 6 - With CLL on ibrutinib with no complete response
20 mg/kg TRU-016 + ibrutinib
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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.
Other Names:
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Experimental: Cohort 7 - With CLL on ibrutinib with stable disease
20 mg/kg TRU-016 + ibrutinib
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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.
Other Names:
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Experimental: Cohort 8 - With relapsed or refractory PTCL
20 mg/kg TRU-016 + 90 mg/m2 bendamustine
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence and severity of adverse events
Time Frame: any time point during the study up to 18 months
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any time point during the study up to 18 months
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CLL Cysteine 481 mutation status
Time Frame: CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.
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The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (<1%).
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CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Response Rate (ORR)
Time Frame: any time point during the study up to 18 months
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any time point during the study up to 18 months
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Progression-free survival (PFS)
Time Frame: any time point during the study up to 18 months
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any time point during the study up to 18 months
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Overall survival (OS)
Time Frame: any time point during the study up to 18 months
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any time point during the study up to 18 months
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Duration of response (DOR)
Time Frame: any time point during the study up to 18 months
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any time point during the study up to 18 months
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Resolution of disease-related symptoms
Time Frame: any time point during the study up to 18 months
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Resolution of disease-related symptoms which are common to the disease include fever, weight loss, night sweats, fatigue, loss of appetite pain, and pruritus; symptoms will be assessed by descriptive statistics and data listings.
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any time point during the study up to 18 months
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Maximum serum drug concentration (Cmax)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Minimum serum drug concentration (Cmin)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Area under the concentration-time curve (AUC0-t and AUC0-∞)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Systemic clearance (CL)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Volume of distribution (Vd)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Elimination half-life (t1/2)
Time Frame: any time point during the study up to 12 months
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any time point during the study up to 12 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Scott C. Stromatt, M.D., Aptevo Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Leukemia, B-Cell
- Lymphoma
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Immunological
- Bendamustine Hydrochloride
- Rituximab
- Obinutuzumab
- Immunoglobulin G
- Idelalisib
Other Study ID Numbers
- 16009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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