Clinical trial NCT02257242: Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: Spectrum Pharmaceuticals, Inc
name: Rhode Island Hospital
name: The Miriam Hospital
First posted: 2014-10-06
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Up to 6 cycles of treatment (approximately 6 months)
Secondary outcomes:
measure: Number of Participants Who Completed Six Cycles of Study Treatment
timeFrame: Up to 6 cycles of treatment (approximately 6 months)
measure: Response Rate
timeFrame: Up to 6 cycles of treatment (approximately 6 months)
measure: Complete Response Rate
timeFrame: Up to 6 cycles of treatment (approximately 6 months)
Other outcomes:
Locations:
city: Providence
country: United States
facility: Rhode Island Hospital and The Miriam Hospital
state: Rhode Island
Study officials:
affiliation: Rhode Island Hospital
name: Adam J Olszewski, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.