The Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma
Phase I Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma
1 other identifier
interventional
10
1 country
7
Brief Summary
The purpose of this study is to test the safety of Venetoclax in combination with FDA approved treatments Bendamustine, Rituximab and Ibrutinib (BR-I). This study will examine the effects Venetoclax has on participants when it is given in combination with BR-I.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for early_phase_1
Started Sep 2017
Longer than P75 for early_phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 20, 2017
CompletedFirst Submitted
Initial submission to the registry
September 25, 2017
CompletedFirst Posted
Study publicly available on registry
September 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 22, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 22, 2024
CompletedMay 13, 2025
January 1, 2024
6.3 years
September 25, 2017
May 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose
1 year
Treatment related toxicity evaluated using CTCAE v4.0
Participants symptoms will be evaluated using CTCAE v4.0
1 years
Study Arms (1)
BR-I in combination with VEN
EXPERIMENTALThe BR-I (bendamustine, rituximab, ibrutinib) regimen will be administered in combination with VEN (Venetoclax).
Interventions
The BR-I (bendamustine, rituximab, ibrutinib) regimen will be administered for six 28-day cycles: bendamustine (90 mg/m2; (or 70mg/m2 for dose level -1); day 1 and 2 ), rituximab (375 mg/m2; day 1), and ibrutinib one pill or four 140mg capsules (560 mg oral daily; day 1-28).
The initial cycle 1 VEN (Venetoclax) dose ramp-up will be: 20 mg daily for 1 week, 50 mg daily for week 2, 100 mg daily for week 3, and 200 mg daily for week 4. Thereafter, VEN will be administered at a fixed dose level of 400 mg daily for varying durations of each 28-day cycle. Now also include a -2 dose level which has the reduced 3-day duration of Ventoclax 400 mg daily.
Eligibility Criteria
You may qualify if:
- Age greater than or equal to 18 years
- Histologically confirmed MCL
- Relapse, refractory or progressive disease following at least 1 line of systemic therapy for mantle cell lymphoma
- ECOG Performance Status \</= 2
- Patients must have completed anticancer treatment with chemotherapy, small molecule inhibitors, immune modulator drugs, biologics, and/or treatment with other anticancer agents at least 3 weeks prior treatment, or 2 weeks if progressing, and recovered from clinically significant toxicity associated with treatment
- ° Palliative radiotherapy must have been discontinued at least 1 week prior to treatment in this study
- Short-course corticosteroids are allowed (≤ 10 days) and must be discontinued prior to study treatment start (Cycle 1, Day 1)
- ° Ongoing administration of a stable dose of corticosteroid therapy (equivalent to ≤ 30 mg prednisone daily and previously received for ≥ 30 days) is permissible provided there is evidence of measurable disease and there will be no increase in steroid dose during the clinical trial
- Patients who have been previously treated with BR or Bendamustine alone are eligible, provided they did not progress during treatment or within 6 months of completing BR or B treatment
- Patients who have been previously treated with ibrutinib or acalabrutinib (or any alternate BTK-inhibitor) are eligible, provided they had evidence of response (at least Stable Disease, Partial Response, or Complete Response) and did not progress within 6 months of treatment initiation
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 2 weeks prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Adequate organ function and laboratory values within the following ranges:
- Absolute neutrophil count \> 1,000 cells/mm3 (1.0 x 109L), if neutropenia is due to bone marrow involvement absolute neutrophil count must be \>/= 500 cells.mm3 (0.5 x 10\^9/L)
- Platelet count \> 75,000 cells/mm3 (75 x 109/L), unless thrombocytopenia is due to bone marrow involvement platelet count must be greater than 25,000 cells/mm3
- Hemoglobin \> 8.0 g/dL
- +12 more criteria
You may not qualify if:
- Prior therapy with venetoclax or alternate BCL-2 inhibitor
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
- Unable to swallow capsules or tablets, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction or other condition that precludes enteral route of administration
- Cerebral/meningeal disease related to the underlying malignancy. Patients with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior central nervous system disease has been definitively treated with no evidence of disease or requirement for steroids
- Active HIV or hepatitis B or C with positive viral load, requiring anti-viral therapy
- Bleeding diathesis or use of warfarin or other vitamin K antagonist
- Prior history of infusion reactions or hypersensitivity to any of the study drugs
- Active concurrent malignancy requiring active therapy
- Pregnant or lactating females
- Prior autologous stem cell transplant within 90 days of study start
- Prior allogenic stem cell transplant within 12 months of study start
- Patients with active graft-versus-host-disease are not eligible
- Patients receiving immunosuppressive therapy for prevention of graft-versus-host-disease are not eligible
- Patients who requires treatment with a potent cytochrome P450 (CYP) 3A inhibitor or inducer
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to Cycle 1, Day 1
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anita Kumar
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 25, 2017
First Posted
September 27, 2017
Study Start
September 20, 2017
Primary Completion
January 22, 2024
Study Completion
January 22, 2024
Last Updated
May 13, 2025
Record last verified: 2024-01