Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma
Phase 1
Completed
- Conditions
- Lymphoma, Mantle-CellLymphoma, Small-CellWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal ZoneLymphoma, Non-HodgkinLymphoma, Follicular
- Interventions
- Registration Number
- NCT02257242
- Lead Sponsor
- Brown University
- Brief Summary
This study evaluates addition of Vincristine Sulfate Liposome Injection (Marqibo®) to the standard regimen of Bendamustine and Rituximab in adult patients with indolent B-cell lymphoma. This is a dose-escalation study.
- Detailed Description
Bendamustine-rituximab is a standard chemotherapy regimen for treatment of many indolent B-cell lymphomas, but most patients experience a recurrence of the lymphoma. Vincristine sulfate has been a traditional component of chemotherapy regimens in non-Hodgkin lymphoma and it is possible that adding it to the bendamustine-rituximab regimen might provide a better quality of remissions or longer duration of remissions with acceptable toxicity.
This is a phase 1, single-center, open-label, single-arm trial in patients with indolent B-cell non-Hodgkin lymphoma otherwise appropriate for bendamustine-rituximab as initial or subsequent line of therapy. Patients will receive the of rituximab and bendamustine in combination with escalating doses of vincristine sulfate liposome injection (Marqibo®). The objective of this study is to assess safety of this combination by establishing the maximum tolerated dose of vincristine sulfate liposome injection (Marqibo®) in the combination.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
Inclusion Criteria
- Histologically confirmed indolent B-cell non-Hodgkin lymphoma.
- Radiological measurable disease.
- Previous treatment for lymphoma is allowed, with the exception of use of bendamustine within 6 months or any prior use of vincristine sulfate liposome injection
- Eastern Cooperative Oncology Group performance status 0 or 1;
- Life expectancy of at least 6 months;
- Adequate organ and marrow function;
- Women of child-bearing potential and men must agree to use adequate contraception.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- History of allergic reactions attributed to any drug used in the study.
- Any lymphoma-directed therapy within 4 weeks.
- Any prior treatment with vincristine sulfate liposome injection.
- Prior treatment with bendamustine or vincristine sulfate within 180 days of enrollment.
- Patients who are receiving any other investigational agents with the exception of endocrine therapy for breast or prostate cancer.
- Central nervous system involvement.
- Peripheral sensory or motor neuropathy.
- History of a demyelinating condition.
- Positive test for the Human Anti-Chimeric Antibody (HACA).
- Patients receiving any medications or substances that are strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzyme are ineligible.
- Uncontrolled intercurrent illness.
- Prisoners.
- Pregnant or breast-feeding women.
- Known Human Immunodeficiency Virus (HIV) or active Hepatitis B infection
- Any prior or active cancer, which in the opinion of the investigator would preclude safe participation in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Vincristine sulfate liposome injection 2.10 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.22 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.8 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.04 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.04 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.8 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.24 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.98 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.14 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.95 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.98 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.19 mg/m^2 Vincristine sulfate liposome injection Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.95 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.8 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.95 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 1.98 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.04 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.10 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.10 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.14 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.14 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.19 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.19 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.22 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.22 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.24 mg/m^2 Bendamustine Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy. Vincristine sulfate liposome injection 2.24 mg/m^2 Rituximab Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose Up to 6 cycles of treatment (approximately 6 months) Determined as the median of the marginal posterior distribution using data from all available patients
- Secondary Outcome Measures
Name Time Method Number of Participants Who Completed Six Cycles of Study Treatment Up to 6 cycles of treatment (approximately 6 months) Response Rate Up to 6 cycles of treatment (approximately 6 months) Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Complete Response Rate Up to 6 cycles of treatment (approximately 6 months) The number of patients achieving complete response during treatment on study
Trial Locations
- Locations (1)
Rhode Island Hospital and The Miriam Hospital
🇺🇸Providence, Rhode Island, United States