Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma (BRiM)
May 12, 2022 updated by: Brown University
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
11
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital and The Miriam Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 1.8 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 1.95 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 1.98 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.04 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.10 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.14 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.19 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.22 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
|
EXPERIMENTAL: Vincristine sulfate liposome injection 2.24 mg/m^2
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.
|
375 mg/m2 I.V. on Day 1 of each cycle
Other Names:
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Other Names:
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Maximum Tolerated Dose
Time Frame: Up to 6 cycles of treatment (approximately 6 months)
|
Determined as the median of the marginal posterior distribution using data from all available patients
|
Up to 6 cycles of treatment (approximately 6 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Participants Who Completed Six Cycles of Study Treatment
Time Frame: Up to 6 cycles of treatment (approximately 6 months)
|
Up to 6 cycles of treatment (approximately 6 months)
|
|
|
Response Rate
Time Frame: 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
|
Up to 6 cycles of treatment (approximately 6 months)
|
|
Complete Response Rate
Time Frame: Up to 6 cycles of treatment (approximately 6 months)
|
The number of patients achieving complete response during treatment on study
|
Up to 6 cycles of treatment (approximately 6 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 10, 2017
Primary Completion (ACTUAL)
August 22, 2020
Study Completion (ACTUAL)
November 18, 2020
Study Registration Dates
First Submitted
September 30, 2014
First Submitted That Met QC Criteria
October 1, 2014
First Posted (ESTIMATE)
October 6, 2014
Study Record Updates
Last Update Posted (ESTIMATE)
February 9, 2023
Last Update Submitted That Met QC Criteria
May 12, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Non-Hodgkin
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Bendamustine Hydrochloride
- Rituximab
- Vincristine
Other Study ID Numbers
- BrUOG 326
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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