A Phase II Evaluation of Bendamustine, Obinutuzumab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Bendamustine
- Conditions
- CCND1 Positive
- Sponsor
- Emory University
- Enrollment
- 23
- Locations
- 3
- Primary Endpoint
- Rate of Complete Response at Completion of Induction Therapy With This Combination
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This phase II trial studies how well bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bendamustine, obinutuzumab, and venetoclax may work better in treating patients with mantle cell lymphoma.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of the combination of bendamustine, obinutuzumab and venetoclax in patients with untreated mantle cell lymphoma. SECONDARY OBJECTIVES: I. To evaluate the safety and dose intensity of the combination of bendamustine, obinutuzumab and venetoclax in untreated mantle cell lymphoma. II. To explore methods of determining molecular remission for patients with untreated mantle cell lymphoma (MCL). III. To evaluate long-term outcomes including progression-free and overall survival for patients with untreated MCL who receive the combination. OUTLINE: Patients receive venetoclax orally (PO) on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine intravenously (IV) on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. After completion of study treatment, patients are followed up at 45-60 days.
Investigators
Jonathon Cohen
Principal Investigator
Emory University
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form
- •Ability and willingness to comply with the requirements of the study protocol
- •Histologic diagnosis of mantle cell lymphoma. This diagnosis must be confirmed at the treating center and patients must have this diagnosis confirmed by at least one of the following criteria:
- •Fluorescent in situ hybridization (FISH) or conventional cytogenetics positive for t(11;14)
- •Cyclin D1 positive by immunohistochemistry
- •Documentation by a hematopathologist at the treating institution that there is pathologic evidence of mantle cell lymphoma if neither criteria above are met
- •No previous therapy for diagnosis of lymphoma (note that in patients deemed to be high-risk for tumor lysis syndrome or for rapid clinical deterioration due to symptomatic disease by the investigator, a short course of steroids designed to decrease tumor burden is permitted)
- •Eastern Cooperative Oncology Group performance status of 0, 1, or 2
- •Hemoglobin ≥ 9 g/dL
- •Absolute neutrophil count ≥ 1.5 x 10⁹/L
Exclusion Criteria
- •History of other malignancy that could affect compliance with the protocol or interpretation of results
- •Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
- •Individuals in documented remission without treatment for ≥ 2 years prior to enrollment may be included at the discretion of the investigator. Patients with more recently treated low risk prostate cancer, thyroid cancer, or ductal carcinoma in situ (DCIS) who are felt to be at low risk for progression and who are not currently taking any chemotherapy, hormonal therapy or other anti-cancer therapy are eligible. Patients who have been treated and been in remission for \< 2 years must be cleared with the study chair prior to initiating study therapy
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
- •Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
- •Received strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of initiating venetoclax. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to first dose of venetoclax
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody
- •Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation
Arms & Interventions
Venetoclax, bendamustine, obinutuzumab
Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.
Intervention: Bendamustine
Venetoclax, bendamustine, obinutuzumab
Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.
Intervention: Obinutuzumab
Venetoclax, bendamustine, obinutuzumab
Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.
Intervention: Venetoclax
Outcomes
Primary Outcomes
Rate of Complete Response at Completion of Induction Therapy With This Combination
Time Frame: Up to 2.5 years from study start
Response will be assessed by positron emission tomography (PET)/computerized tomography (CT) imaging according to the Lugano Classification for response assessment in lymphoma, developed at the 2014 International Conference on Malignant Lymphoma.
Secondary Outcomes
- Rate of Minimal Residual Disease (MRD) Negative Complete Response by ClonoSEQ Mantle Cell Lymphoma (MCL) Assay(Up to 6 years from study start)
- Overall Response Rate(Up to 6 years from study start)
- Time to Tumor Progression(Up to 6 years from study start)
- Progression Free Survival (PFS)(Up to 6 years from study start)
- Overall Survival(Up to 6 years from study start)