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

Sponsor

Adam Olszewski (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02257242

Collaborator

Spectrum Pharmaceuticals, Inc (Industry), Rhode Island Hospital (Other), The Miriam Hospital (Other)

Enrollment

Location

Arm

51.7

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin Lymphoma, Follicular Lymphoma, Mantle-Cell Lymphoma, Small-Cell Waldenstrom Macroglobulinemia Lymphoma, B-Cell, Marginal Zone	Drug: Rituximab Drug: Bendamustine Drug: Vincristine sulfate liposome injection	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2017

Actual Primary Completion Date :

Aug 22, 2020

Anticipated Study Completion Date :

Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose-escalation cohort 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.	Drug: Rituximab 375 mg/m2 I.V. on Day 1 of each cycle Other Names: Rituxan, anti-CD20 antibody Drug: Bendamustine 90 mg/m2 I.V. on Day 1 and 2 of each cycle Other Names: Treanda Drug: Vincristine sulfate liposome injection Dose per dose escalation protocol, I.V. on Day 2 of each cycle Other Names: Marqibo

Arm

Intervention/Treatment

Experimental: Dose-escalation cohort

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.

Drug: Rituximab

375 mg/m2 I.V. on Day 1 of each cycle

Other Names:

Rituxan, anti-CD20 antibody

Drug: Bendamustine

90 mg/m2 I.V. on Day 1 and 2 of each cycle

Other Names:

Treanda

Drug: Vincristine sulfate liposome injection

Dose per dose escalation protocol, I.V. on Day 2 of each cycle

Other Names:

Marqibo

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose [Calculated within 6 months of the enrollment of the last subject - by December 2017]
Determined as the median of the marginal posterior distribution using data from all available patients

Secondary Outcome Measures

Cumulative toxicity rate [Calculated within 6 months of the enrollment of the last subject - by December 2017]
Cumulative rate of adverse effects during treatment on study
Rate of treatment completion [Calculated within 6 months of the enrollment of the last subject - by December 2017]
Proportion of patients completing the six planned cycles of study treatment
Response rate [Calculated within 6 months of the enrollment of the last subject - by December 2017]
The proportion of patients achieving at least partial response during treatment on study
Complete response rate [Calculated within 6 months of the enrollment of the last subject - by December 2017]
The proportion of patients achieving complete response during treatment on study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.