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

  • United States
    • 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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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

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

Brown University

Collaborators

The Miriam Hospital
Rhode Island Hospital
Spectrum Pharmaceuticals, Inc

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.

General Publications

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

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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