Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma (BRiM)

Brown University

Status and phase: Completed; Phase 1

Conditions: Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Small-Cell; Lymphoma, Non-Hodgkin

Treatments: Drug: Vincristine sulfate liposome injection; Drug: Bendamustine; Drug: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02257242

BrUOG 326

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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11 participants in 9 patient groups

Vincristine sulfate liposome injection 1.8 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 1.95 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 1.98 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.04 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.10 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.14 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.19 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.22 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection

Vincristine sulfate liposome injection 2.24 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Vincristine sulfate liposome injection