A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Overview
- Phase
- Phase 1
- Intervention
- Obinutuzumab
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 54
- Locations
- 4
- Primary Endpoint
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
- Status
- Active, Not Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Detailed Description
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the best order of administration of these two drugs. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved ibrutinib and obinutuzumab individually for the treatment of patients with Chronic Lymphocytic Leukemia, your type of cancer. However, the FDA has not approved the combination of these two drugs as a treatment for any disease. Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a type of protein called a kinase that helps leukemia cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing. Obinutuzumab is a type of drug called a monoclonal antibody. It is believed to attach to a protein called CD20 on the outside of a Chronic Lymphocytic Leukemia cell. By attaching to the cell, the antibody can cause the Chronic Lymphocytic Leukemia cell to die. In this research study, the investigators are assessing the safety of various dosing regimens of ibrutinib and obinutuzumab. The investigators are trying to determine whether it is better to give one drug before the other or if they can be started at the same time.
Investigators
Matthew S. Davids, MD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •Prior treatment with either obinutuzumab or ibrutinib
- •History of other malignancies, except:
- •Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- •Adequately treated carcinoma in situ without evidence of disease.
- •Low-risk prostate cancer on active surveillance
- •Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of \>20 mg/day of prednisone) within 28 days of the first dose of study drug.
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- •Recent infection requiring systemic treatment that was completed ≤7 days before the first dose of study drug.
Arms & Interventions
Arm A- obinutuzumab -> ibrutinib
Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.
Intervention: Obinutuzumab
Arm A- obinutuzumab -> ibrutinib
Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.
Intervention: Ibrutinib
Arm B- ibrutinib -> obinutuzumab
Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7
Intervention: Obinutuzumab
Arm B- ibrutinib -> obinutuzumab
Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7
Intervention: Ibrutinib
Arm C- obinutuzumab/ibrutinib
Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.
Intervention: Obinutuzumab
Arm C- obinutuzumab/ibrutinib
Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Baseline to 6 Months
To assess the safety of 3 different dosing regimens of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL
Secondary Outcomes
- Duration of Response(2 Years)
- Complete Response Rate(6 Months)
- Overall Response Rate(2 Years)
- Minimal residual disease (MRD) status in the bone marrow and blood(6 Months)
- Progression Free Survival(2 Years)
- Partial Response Rate(6 Months)