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

BrUOG 326: A Phase I Dose-Escalation Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With Bendamustine and Rituximab (BRiM) in Indolent Non-Hodgkin Lymphoma

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.

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.

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.