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

Primary Purpose

Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Bendamustine
Vincristine sulfate liposome injection
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Bendamustine, Rituximab, Vincristine sulfate, Vincristine sulfate liposome injection, Phase I, Escalation With Overdose Control

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Rhode Island Hospital and The Miriam Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Vincristine sulfate liposome injection 1.8 mg/m^2

Vincristine sulfate liposome injection 1.95 mg/m^2

Vincristine sulfate liposome injection 1.98 mg/m^2

Vincristine sulfate liposome injection 2.04 mg/m^2

Vincristine sulfate liposome injection 2.10 mg/m^2

Vincristine sulfate liposome injection 2.14 mg/m^2

Vincristine sulfate liposome injection 2.19 mg/m^2

Vincristine sulfate liposome injection 2.22 mg/m^2

Vincristine sulfate liposome injection 2.24 mg/m^2

Arm 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 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 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 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 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 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 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 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 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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose
Determined as the median of the marginal posterior distribution using data from all available patients

Secondary Outcome Measures

Number of Participants Who Completed Six Cycles of Study Treatment
Response Rate
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
Complete Response Rate
The number of patients achieving complete response during treatment on study

Full Information

First Posted
September 30, 2014
Last Updated
May 12, 2022
Sponsor
Brown University
Collaborators
Spectrum Pharmaceuticals, Inc, Rhode Island Hospital, The Miriam Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02257242
Brief Title
Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma
Acronym
BRiM
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
May 10, 2017 (Actual)
Primary Completion Date
August 22, 2020 (Actual)
Study Completion Date
November 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brown University
Collaborators
Spectrum Pharmaceuticals, Inc, Rhode Island Hospital, The Miriam Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Small-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone
Keywords
Bendamustine, Rituximab, Vincristine sulfate, Vincristine sulfate liposome injection, Phase I, Escalation With Overdose Control

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vincristine sulfate liposome injection 1.8 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 1.95 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 1.98 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.04 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.10 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.14 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.19 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.22 mg/m^2
Arm Type
Experimental
Arm 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.
Arm Title
Vincristine sulfate liposome injection 2.24 mg/m^2
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, anti-CD20 antibody
Intervention Description
375 mg/m2 I.V. on Day 1 of each cycle
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
90 mg/m2 I.V. on Day 1 and 2 of each cycle
Intervention Type
Drug
Intervention Name(s)
Vincristine sulfate liposome injection
Other Intervention Name(s)
Marqibo
Intervention Description
Dose per dose escalation protocol, I.V. on Day 2 of each cycle
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
Determined as the median of the marginal posterior distribution using data from all available patients
Time Frame
Up to 6 cycles of treatment (approximately 6 months)
Secondary Outcome Measure Information:
Title
Number of Participants Who Completed Six Cycles of Study Treatment
Time Frame
Up to 6 cycles of treatment (approximately 6 months)
Title
Response Rate
Description
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
Time Frame
Up to 6 cycles of treatment (approximately 6 months)
Title
Complete Response Rate
Description
The number of patients achieving complete response during treatment on study
Time Frame
Up to 6 cycles of treatment (approximately 6 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam J Olszewski, MD
Organizational Affiliation
Rhode Island Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital and The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35641232
Citation
Ollila T, Butera J, Egan P, Reagan J, Thomas A, Yakirevich I, MacKinnon K, Margolis J, McMahon J, Rosati V, Olszewski AJ. Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as First-Line Therapy for B-Cell Lymphomas: A Phase I Study. Oncologist. 2022 Jul 5;27(7):532-e542. doi: 10.1093/oncolo/oyab079.
Results Reference
derived

Learn more about this trial

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

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