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
| Registry | NCT02257242, acronym BRiM |
|---|---|
| Status | Completed |
| Phase | Phase 1 |
| Study type | Interventional; randomized, sequential, masking: none, treatment |
| Enrollment | 11 (Actual) |
| Sponsor | Brown University (Other); collaborators: Spectrum Pharmaceuticals, Inc, Rhode Island Hospital, The Miriam Hospital |
| Conditions | Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Small-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone |
| Interventions | Rituximab, Bendamustine, Vincristine sulfate liposome injection (Drug) |
| Dates | start 2017-05-10, primary completion 2020-08-22, completion 2020-11-18, first posted 2014-10-06, last updated 2023-02-09 |
| Locations | 1 site in United States |
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All trials for Lymphoma, Non-Hodgkin All trials for Lymphoma, Follicular All trials of Rituximab All trials of Bendamustine
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.
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Vincristine sulfate liposome injection 1.8 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 1.95 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 1.98 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.04 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.10 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.14 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.19 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.22 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
| Vincristine sulfate liposome injection 2.24 mg/m^2 | Experimental | Drug: Rituximab; Drug: Bendamustine; Drug: Vincristine sulfate liposome injection | 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. |
Sex: All, ages: 18 Years to any
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.
| Milestone | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Started | 2 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 |
| Completed | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 |
| Not completed | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Time frame: Adverse event data was collected from the date the subject signed the informed consent form for the trail until the end of study visit, approximately 6 months.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Vincristine Sulfate Liposome Injection: 1.8 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 1.95 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 1.98 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.04 mg/m^2 | 0/2 (0.0%) | 1/2 (50.0%) | 2/2 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.1 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.14 mg/m^2 | 0/1 (0.0%) | 1/1 (100.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.19 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.22 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Vincristine Sulfate Liposome Injection: 2.24 mg/m^2 | 0/1 (0.0%) | 0/1 (0.0%) | 1/1 (100.0%) |
| Term | Organ system | 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: 2.1 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | 0/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Fever | General disorders | 0/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Ileus | Gastrointestinal disorders | 0/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Thromboembolic Event | Vascular disorders | 0/1 | 0/1 | 0/1 | 0/2 | 0/1 | 1/1 | 0/1 | 0/1 | 0/1 |
| Term | Organ system | 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: 2.1 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0/1 | 1/1 | 1/1 | 1/2 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Alanine aminotransferase increased | Investigations | 0/1 | 1/1 | 1/1 | 1/2 | 0/1 | 1/1 | 0/1 | 1/1 | 0/1 |
| Alkaline phosphatase increased | Investigations | 1/1 | 0/1 | 1/1 | 1/2 | 0/1 | 0/1 | 1/1 | 1/1 | 0/1 |
| Alopecia | Skin and subcutaneous tissue disorders | 1/1 | 1/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Anemia | Blood and lymphatic system disorders | 1/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 1/1 | 1/1 | 0/1 |
| Anorexia | Metabolism and nutrition disorders | 0/1 | 0/1 | 0/1 | 0/2 | 1/1 | 0/1 | 1/1 | 0/1 | 0/1 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1/1 | 0/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Aspartate aminotransferase increased | Investigations | 0/1 | 0/1 | 1/1 | 1/2 | 1/1 | 1/1 | 0/1 | 0/1 | 1/1 |
| Bone pain | Musculoskeletal and connective tissue disorders | 0/1 | 0/1 | 0/1 | 0/2 | 0/1 | 0/1 | 1/1 | 0/1 | 1/1 |
| Chills | General disorders | 1/1 | 1/1 | 0/1 | 1/2 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Constipation | Gastrointestinal disorders | 1/1 | 1/1 | 1/1 | 1/2 | 1/1 | 1/1 | 1/1 | 0/1 | 0/1 |
| Dehydration | Metabolism and nutrition disorders | 1/1 | 0/1 | 0/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Diarrhea | Gastrointestinal disorders | 0/1 | 0/1 | 1/1 | 1/2 | 0/1 | 0/1 | 0/1 | 1/1 | 0/1 |
| Dyspepsia | Gastrointestinal disorders | 1/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Dysgeusia | Nervous system disorders | 1/1 | 0/1 | 0/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1/1 | 0/1 | 0/1 | 1/2 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Fatigue | General disorders | 0/1 | 1/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Fever | General disorders | 1/1 | 1/1 | 0/1 | 2/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Headache | Nervous system disorders | 0/1 | 1/1 | 0/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hiccups | Respiratory, thoracic and mediastinal disorders | 1/1 | 0/1 | 0/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hoarseness | Respiratory, thoracic and mediastinal disorders | 0/1 | 0/1 | 1/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hypocalcemia | Metabolism and nutrition disorders | 1/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hyponatremia | Metabolism and nutrition disorders | 1/1 | 1/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hypophosphatemia | Metabolism and nutrition disorders | 1/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Hypertension | Vascular disorders | 1/1 | 0/1 | 0/1 | 2/2 | 0/1 | 1/1 | 1/1 | 1/1 | 1/1 |
| Ileus | Gastrointestinal disorders | 0/1 | 0/1 | 0/1 | 1/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Infusion related reaction | Injury, poisoning and procedural complications | 1/1 | 1/1 | 0/1 | 1/2 | 0/1 | 1/1 | 1/1 | 0/1 | 1/1 |
| Insomnia | Psychiatric disorders | 0/1 | 0/1 | 0/1 | 0/2 | 1/1 | 1/1 | 0/1 | 0/1 | 1/1 |
| Lymphocyte count decreased | Investigations | 1/1 | 1/1 | 1/1 | 2/2 | 1/1 | 0/1 | 1/1 | 1/1 | 1/1 |
| Mucosal infection | Infections and infestations | 0/1 | 0/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1/1 | 1/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Nausea | Gastrointestinal disorders | 1/1 | 1/1 | 1/1 | 0/2 | 1/1 | 0/1 | 1/1 | 1/1 | 1/1 |
| Neck edema | General disorders | 0/1 | 1/1 | 0/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Neutrophil count decreased | Investigations | 1/1 | 0/1 | 1/1 | 1/2 | 1/1 | 0/1 | 1/1 | 0/1 | 0/1 |
| Peripheral sensory neuropathy | Nervous system disorders | 1/1 | 1/1 | 1/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Platelet count decreased | Investigations | 1/1 | 0/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| Pruritus | Skin and subcutaneous tissue disorders | 0/1 | 1/1 | 0/1 | 0/2 | 0/1 | 0/1 | 1/1 | 0/1 | 0/1 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 0/1 | 0/1 | 0/1 | 1/2 | 1/1 | 1/1 | 1/1 | 0/1 | 0/1 |
| Skin infection | Infections and infestations | 1/1 | 0/1 | 1/1 | 0/2 | 0/1 | 0/1 | 0/1 | 1/1 | 0/1 |
| Urinary frequency | Renal and urinary disorders | 1/1 | 0/1 | 1/1 | 0/2 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Vomiting | Gastrointestinal disorders | 0/1 | 1/1 | 0/1 | 0/2 | 1/1 | 0/1 | 0/1 | 1/1 | 0/1 |
| Weight loss | Investigations | 1/1 | 0/1 | 0/1 | 1/2 | 1/1 | 0/1 | 0/1 | 0/1 | 1/1 |
| White blood cell decreased | Investigations | 1/1 | 0/1 | 1/1 | 1/2 | 1/1 | 0/1 | 1/1 | 0/1 | 0/1 |
| Facility | City | Country | Status |
|---|---|---|---|
| Rhode Island Hospital and The Miriam Hospital | Providence, Rhode Island | United States |