Bendamustine + Obinutuzumab Induction Chemoimmunotherapy With Risk-adapted Obinutuzumab Maintenance Therapy in Previously Untreated Mantle Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Bendamustine
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- University of Wisconsin, Madison
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS) at 2 Years
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This is a phase II single-arm, open-label, multicenter study evaluating the efficacy and safety of the combination of induction chemoimmunotherapy with bendamustine and obinutuzumab (BO) followed by consolidation therapy and maintenance therapy with obinutuzumab in subjects who have not received prior cytotoxic chemotherapy for their Mantle Cell Lymphoma (MCL) (i.e., prior single agent rituximab is permitted, prior involved-field radiotherapy is permitted).
Detailed Description
This is a phase II single-arm, open-label, multicenter study evaluating the efficacy and safety of the combination of induction chemoimmunotherapy with bendamustine and obinutuzumab (BO) followed by consolidation therapy and maintenance therapy with obinutuzumab in subjects who have not received prior cytotoxic chemotherapy for their MCL (i.e., prior single-agent rituximab is permitted, prior involved-field radiotherapy is permitted). Therapy for individual subjects will be risk-adapted based on results of minimal residual disease (MRD) testing performed after the consolidation phase. The study will be carried out at the University of Wisconsin Carbone Cancer Center (UWCCC) and participating community and academic practice sites within the Wisconsin Oncology Network (WON). There will be 6-10 sites participating in this study. The subject participation will include a screening period, treatment period, and a follow-up period. The induction chemoimmunotherapy regimen consists of bendamustine and obinutuzumab for 4-6 cycles, followed by consolidation and maintenance therapy with obinutuzumab in subjects achieving an objective response to induction therapy (i.e., complete or partial response; stable disease with objective evidence of tumor shrinkage. Subjects who are MRD-negative (determined by MRD testing on bone marrow and PB) after consolidation therapy will omit maintenance therapy. Subjects will undergo disease reassessment after C4 of induction BO chemoimmunotherapy, after obinutuzumab consolidation therapy, and after C4 and C8 of maintenance obinutuzumab. MRD testing will be done after C2 of induction (PB only), after consolidation (BMA and PB), and post-maintenance or end of treatment (EOT) (PB only).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years at the time of signing the informed consent document.
- •Histologically confirmed mantle cell lymphoma (confirmation of cyclin D1 positivity on diagnostic biopsy).
- •Subjects must have at least one bi-dimensionally measurable lesion; one of the measurements must be ≥1.5 cm in one direction
- •No prior cytotoxic chemotherapy; prior therapy with single-agent rituximab is permitted. Prior involved-field radiotherapy to symptomatic nodal sites of involvement is also permitted.
- •Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease.
- •Must meet one of the following criteria:
- •Not eligible for more intensive cytotoxic chemotherapy or consolidative autologous stem cell transplant based on one or more of the following:
- •Clinically significant heart or lung comorbidities, as reflected by at least 1 of the following:
- •Left ventricular ejection fraction (LVEF) ≤ 50%
- •Chronic stable angina or congestive heart failure controlled with medication
Exclusion Criteria
- •Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.
- •Concurrent use of other anti-cancer agents or treatments.
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment.
- •Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years.
- •Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other mAb therapy.
- •Known to be positive for HIV or infectious hepatitis (type B or C).
- •Pregnant or breast-feeding females.
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
Arms & Interventions
Bendamustine + Obinutuzumab (BO)
Induction chemoimmunotherapy (28 day cycles): Bendamustine 90 mg/m2 IV days 1 \& 2 every 28 days X 4-6 cycles Obinutuzumab: * Cycle 1: 100 mg IV day 1, 900 mg IV day 2, 1000 mg IV days 8 \& 15 * Cycles 2-6: 1000 mg IV day 1 Consolidation phase: Obinutuzumab 1000 mg IV weekly X 4 doses Maintenance phase (8 week cycles): Obinutuzumab 1000 mg IV on day 1 of cycles 1-8
Intervention: Bendamustine
Bendamustine + Obinutuzumab (BO)
Induction chemoimmunotherapy (28 day cycles): Bendamustine 90 mg/m2 IV days 1 \& 2 every 28 days X 4-6 cycles Obinutuzumab: * Cycle 1: 100 mg IV day 1, 900 mg IV day 2, 1000 mg IV days 8 \& 15 * Cycles 2-6: 1000 mg IV day 1 Consolidation phase: Obinutuzumab 1000 mg IV weekly X 4 doses Maintenance phase (8 week cycles): Obinutuzumab 1000 mg IV on day 1 of cycles 1-8
Intervention: Obinutuzumab
Outcomes
Primary Outcomes
Progression Free Survival (PFS) at 2 Years
Time Frame: Up to 2 years
For each patient, progression-free survival (PFS) is measured from cycle 1 day 1 (C1D1) of induction chemoimmunotherapy to the day patient experiences an event of disease progression or death, whichever occurs first. If a patient has not experienced an event at the time of analysis, patient's data will be censored at the date of the last available evaluation. The 2-year PFS probability will be estimated using the Kaplan-Meier method. From the date of C1D1 of induction therapy to the date of progression or death; in the absence of progression or death, participants will be followed for a minimum of 24 months after completion of study-related treatment. PFS rates at 2 years are reported here.
Secondary Outcomes
- Minimal Residual Disease (MRD) Status(At the end of Cycle 2 of induction therapy (each cycle is 28 days), following consolidation phase (after 6 cycles of induction, consolidation is 4 weekly doses of obinutuzumab), within 30 days of completing protocol therapy (up to 15 months total))
- Estimate the Concordance Rate Between Peripheral Blood (PB) and Bone Marrow Aspirates (BMA) in Predicting MRD Status.(At the end of Cycle 2 of induction therapy (each cycle is 28 days), following consolidation phase of therapy (after 6 cycles of induction, consolidation is 4 weekly doses of obinutuzumab), and within 30 days of completing protocol therapy)
- Determine Objective Response Rates (CR + PR) With Induction Bendamustine and Obinutuzumab (BO) in Previously Untreated MCL Using the Lugano Classification for Response in Lymphoma(Assessed up to cycle 8 of maintenance therapy, up to 15 months on study)
- Overall Survival (OS)(Up to 3 years)
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 During Therapy Induction BO Chemoimmunotherapy and Obinutuzumab Consolidation and Maintenance(Up to 25 months (until 30 days after completion of final dose of study-related treatment))