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The Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03295240
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : September 28, 2018
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Lymphoma Drug: BR-I (bendamustine, rituximab, ibrutinib) Drug: VEN (Venetoclax) Early Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : September 20, 2019
Estimated Study Completion Date : September 20, 2019


Arm Intervention/treatment
Experimental: BR-I in combination with VEN
The BR-I (bendamustine, rituximab, ibrutinib) regimen will be administered in combination with VEN (Venetoclax).
Drug: BR-I (bendamustine, rituximab, ibrutinib)
The BR-I (bendamustine, rituximab, ibrutinib) regimen will be administered for six 28-day cycles: bendamustine (90 mg/m2; day 1 and 2), rituximab (375 mg/m2; day 1), and ibrutinib (560 mg oral daily; day 1-28).

Drug: VEN (Venetoclax)
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.




Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: 1 year ]
  2. Treatment related toxicity evaluated using CTCAE v4.0 [ Time Frame: 1 years ]
    Participants symptoms will be evaluated using CTCAE v4.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 18 years
  • Histologically confirmed MCL
  • Relapse or progression after at least one systemic therapy for mantle cell lymphoma
  • Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment in this study. If there is progression of disease on that therapy and all adverse effects have resolved to Grade 1 or baseline, in which case 2 weeks is acceptable.
  • Palliative radiotherapy must have been discontinued 1 week prior to treatment in this study
  • 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.
  • ECOG Performance Status 0-2
  • Short-course corticosteroids are permissible in the following circumstances

    • Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (< 10 days) must have been discontinued prior to study treatment
    • 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.
  • 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), if thrombocytopenia I due to bone marrow involvement platelet count must be 50,000 cells/mm3
  • Hemoglobin > 8.0 g/dL
  • Serum aspartate transaminase (AST) and alanine transaminase (ALT) </= 2.5 x upper limit of normal (ULN)
  • Estimate creatinine clearance (Cockcroft-Gault) >60 mL/min
  • Bilirubin <1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Patients who have been previously treated with BR are eligible, provided they did not progress during or within 6 months of completing BR treatment
  • Patients who have undergone autologous stem cell transplant more than 3 months prior are eligible
  • Patients who have undergone allogeneic stem cell transplant within 12 months, without active graft-versus-host-disease, and not on immunosuppression for prevention of graft-versus-host disease are eligible
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab, whichever is longer

    • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>/= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
    • Examples of contraceptive method with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:

    • With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of rituximab. Men must refrain from donating sperm during this same period.
    • With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of rituximab to avoid exposing the embryo.
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Prior therapy with ibrutinib or venetoclax
  • 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, 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
  • CNS involvement of the patient‟s lymphoma
  • 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
  • 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 4 weeks prior to Cycle 1, Day 1
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03295240


Contacts
Contact: Anita Kumar, MD 212-639-2668 kumara2@mskcc.org
Contact: Anas Younes, MD 212-639-5059 younesa@mskcc.org

Locations
United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Anita Kumar, MD    212-639-2668      
Memoral Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Anita Kumar, MD    212-639-2668      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Anita Kumar, MD    212-639-2668      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Anita Kumar, MD    212-639-2668      
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Anita Kumar, MD    212-639-2668      
Memorial Sloan Kettering @ Rockville Recruiting
Rockville Centre, New York, United States, 11570
Contact: Anita Kumar, MD    212-639-2668      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03295240     History of Changes
Other Study ID Numbers: 17-216
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Mantle Cell Lymphoma
MCL
Lymphoma
Venetoclax
17-216

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Venetoclax
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action