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Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01415752
First received: August 11, 2011
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.


Condition Intervention Phase
Lymphoma
Neurotoxicity
Therapy-related Toxicity
Biological: rituximab
Drug: bendamustine hydrochloride
Drug: bortezomib
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 2-year PFS rate of patients treated with RBV to an induction regimen of RB compared to RB alone [ Designated as safety issue: No ]
  • PFS improvement of patients treated with lenalidomide added to a consolidation regimen [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PET-documented CR rate [ Designated as safety issue: No ]
  • Response rate to RB and RBV [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 332
Study Start Date: May 2012
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm E.
Biological: rituximab
Given IV
Drug: bendamustine hydrochloride
Given IV
Experimental: Arm B
Patients receive induction therapy comprising bortezomib IV subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm F.
Biological: rituximab
Given IV
Drug: bendamustine hydrochloride
Given IV
Drug: bortezomib
Given IV or SC
Experimental: Arm C
Patients receive induction therapy comprising rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm G.
Biological: rituximab
Given IV
Drug: bendamustine hydrochloride
Given IV
Drug: lenalidomide
Given PO
Experimental: Arm D
Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm H.
Biological: rituximab
Given IV
Drug: bendamustine hydrochloride
Given IV
Drug: bortezomib
Given IV or SC
Drug: lenalidomide
Given PO
Experimental: Arm E
Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Experimental: Arm F
Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Experimental: Arm G
Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Drug: lenalidomide
Given PO
Experimental: Arm H
Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Drug: lenalidomide
Given PO

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
  • Patients must have at least one objective measurable disease parameter

    • Abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
    • Measurable disease in the liver is required if the liver is the only site of lymphoma
  • Patient must have no CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mcL (1.5 x 10^9/L)*
  • Platelets ≥ 100,000/mcL (100 x 10^9/L)* NOTE: *Unless due to marrow involvement.
  • AST/ALT ≤ 2 times upper limit of normal (ULN)
  • Bilirubin ≤ 2 times ULN
  • Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
  • Women (sexually mature female) must not be pregnant or breast-feeding
  • Negative pregnancy test
  • Women of childbearing potential and sexually active males use an accepted and effective method of contraception

    • Men must agree to use a latex condom during sexual contact with a female of child-bearing potential, even if they have had a successful vasectomy
    • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, or any surgically or radiation-cured malignancy continuously disease free for ≥ 5 years so as not to interfere with interpretation of radiographic response
  • Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they must register into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

    • Patients must have no medical contra-indications to, and be willing to take, deep vein thrombosis (DVT) prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have DVT prophylaxis

      • Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have therapeutic doses of low-molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0
      • Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis

        • Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment
    • Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment
    • Males must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment
  • HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:

    • HIV is sensitive to antiretroviral therapy
    • Must be willing to take effective antiretroviral therapy, if indicated
    • No history of CD4 prior to or at the time of lymphoma diagnosis < 300 cells/mm³
    • No history of AIDS-defining conditions
    • If on antiretroviral therapy, must not be taking zidovudine or stavudine
    • Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later
  • Patients must not have grade 2 or greater peripheral neuropathy
  • Patients must not have NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
  • Patients must not have hypersensitivity to bortezomib, boron, or mannitol
  • Patients must not have a serious medical or psychiatric illness likely to interfere with study participation

PRIOR CONCURRENT THERAPY:

  • No prior therapy for MCL, except < 1 week of steroid therapy for symptom control
  • HIV-positive patients are not excluded, but to enroll, must meet all of the below criteria:

    • Must be willing to take effective antiretroviral therapy if indicated
    • If on antiretroviral therapy, must not be taking zidovudine or stavudine
  • Patients must not be participating in any other clinical trial or taking any other experimental medications within 14 days prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01415752

  Show 190 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Mitchell R. Smith, MD, PhD Fox Chase Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01415752     History of Changes
Other Study ID Numbers: CDR0000707057, ECOG-E1411, NCI-2011-02980
Study First Received: August 11, 2011
Last Updated: October 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
neurotoxicity
therapy-related toxicity
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neurotoxicity Syndromes
Chemically-Induced Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Nervous System Diseases
Poisoning
Bendamustine
Bortezomib
Lenalidomide
Nitrogen Mustard Compounds
Rituximab
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors

ClinicalTrials.gov processed this record on November 24, 2014