Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Refractory or Relapsed Indolent Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
Celgene Corporation
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier:
NCT01429025
First received: September 2, 2011
Last updated: July 18, 2013
Last verified: July 2013
  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. Lenalidomide may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. Giving lenalidomide together with rituximab and bendamustine hydrochloride may kill more cancer cells.

PURPOSE: This phase I trial studies the side effects and the best dose of giving lenalidomide together with rituximab and bendamustine hydrochloride in treating patients with refractory or relapsed indolent non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: bendamustine hydrochloride
Drug: lenalidomide
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot/Feasibility Phase I Study of Bendamustine, Rituximab and Lenalidomide in Patients With Refractory/Relapsed Indolent NHL

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Maximum-tolerated dose of lenalidomide in combination with bendamustine hydrochloride and rituximab [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity profile [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: Time from registration to the earliest date of documented disease progression or death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Overall response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: May 2012
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab, bendamustine and lenalidomide
Patients receive rituximab IV on day 1, bendamustine hydrochloride IV on days 1-2, and lenalidomide PO on days 1-10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
IV
Drug: bendamustine hydrochloride
IV
Drug: lenalidomide
PO
Other: laboratory biomarker analysis

Detailed Description:

OBJECTIVES:

Primary

  • To establish the maximum-tolerated dose of lenalidomide in combination with bendamustine hydrochloride (B) and rituximab (R) chemotherapy.

Secondary

  • To evaluate the toxicity profile of lenalidomide in combination with BR chemotherapy.
  • To assess progression-free survival.
  • To assess the overall and complete response rates of lenalidomide in combination with BR in patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL).

Tertiary

  • To explore changes of immune microenvironment - cytokine profile with therapy and relation to the outcome.
  • To explore biological factors associated with therapy and therapy outcome (the tumor tissue and blood specimens will be banked for future exploratory studies).
  • To assess impact of statin use on response to therapy and patient outcome. (Exploratory)
  • To store serum for vitamin D assessment and correlate the levels with outcome. (Exploratory)
  • To record any transformation to aggressive NHL events and perform exploratory studies of association of tumor-immune microenvironment, histology, and expression of DNA damaging and repair enzymes with transformation.

OUTLINE: This is a multicenter, dose-escalation study of lenalidomide.

Patients receive rituximab IV over 5-8 hours on day 1, bendamustine hydrochloride IV over 30-60 minutes on days 1-2, and lenalidomide orally (PO) on days 1-10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection at baseline and periodically during treatment for correlative studies. Tumor tissue samples may also be collected.

After completion of study treatment, patients are followed up for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed relapsed (recurrent after previous therapies) or refractory (no response to previous therapy), indolent/low-grade B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen

    • Small lymphocytic lymphoma (SLL) excluding chronic lymphocytic leukemia (CLL) (patients with peripheral blood lymphocyte count > 5,000/mm³)
    • Follicular lymphoma, grades 1, 2 (grade 3 excluded)
    • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue (MALT) type
    • Lymphoplasmacytic lymphoma including Waldenstrom macroglobulinemia
  • The biopsy-confirming relapse can be up to 12 weeks prior to registration as long as there is no intervening therapy; if patients have been on active treatment within last 12 weeks, the tumor biopsy must be repeated before study enrollment to evaluate for transformation
  • Measurable disease (at least 1 lesion of ≥ 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron (PET)/CT

    • Patients with Waldenstrom macroglobulinemia are not required to have measurable disease by CT or PET/CT if monoclonal protein is detectable by serum protein electrophoresis and/or IgM level is at least 2 times upper limit of normal
  • No active CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
  • No known myelodysplastic syndrome

PATIENT CHARACTERISTICS:

  • ECOG performance status 0, 1, or 2
  • Life expectancy ≥ 6 months
  • ANC ≥ 1,500/mL
  • Platelet count ≥ 100,000/mL
  • Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN) OR, if total bilirubin is > 1.5 times ULN, the direct bilirubin must be normal
  • SGOT (AST) ≤ 5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

    • Females of childbearing potential (FCBP) must have:

      • A negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL ≤ 10 - 14 days prior to registration and again ≤ 24 hours prior to starting course 1 of lenalidomide
      • ≥ 28 days prior to registration, throughout the duration of the study, and for up to 28 days from the last dose of lenalidomide, FBCP must agree to either continued abstinence from heterosexual intercourse or must begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME
      • Must agree to ongoing pregnancy testing throughout the duration of the study and for up to 28 days from the last dose of lenalidomide
    • Men must agree to abstinence or to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
  • Willing to return to North Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
  • Ability to swallow oral medications
  • If currently not on anticoagulation medication, willing and able to take low-dose aspirin (81 mg) daily
  • Any of the following not allowed:

    • Pregnant women
    • Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No prior AIDS-defining conditions

    • HIV-positive patients without history of AIDS-defining conditions are eligible if CD4 cells < 400/mm³
  • No uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No other active malignancy requiring concomitant active therapy such as radiation, chemotherapy, or immunotherapy; exceptions to this are as follows:

    • Localized non-melanotic skin cancer
    • Cancers that are inactive that are being treated with hormonal therapy
    • Any cancer that, in the judgment of the investigator, will not interfere with the study treatment plan and response assessment or require concomitant anticancer therapy for the duration of this study
  • No history of myocardial infarction ≤ 6 months or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Patients with a history of life-threatening (i.e., pulmonary embolism), deep vein thrombosis (DVT), or recurrent thrombosis/embolism who are not on or unwilling to receive anticoagulation are excluded

    • Patients with history of DVT or life-threatening or recurrent thrombosis/embolism (PE) may enter the study but must receive anticoagulation with low molecular weight (LMW) heparin or therapeutic warfarin during the protocol treatment and for ≥ 6 months afterwards
    • Patients with a history (> 6 months prior to study entry) of a non-life-threatening, provoked thrombosis (e.g., history of catheter-related thrombus or similar) and without known thrombophilia can participate in the study and receive standard prophylaxis with aspirin or LMW heparin/warfarin at the discretion of treating MD

PRIOR CONCURRENT THERAPY:

  • If currently not on anticoagulation medication, willing and able to take low-dose aspirin (≥ 81 mg) daily

    • The dose of aspirin should be a minimum of 81 mg and can be higher if the patient is on the agent for other reasons
    • If aspirin is contraindicated, the patient may be considered for the study after consultation with the study chair regarding other alternatives, including the possible use of warfarin or low molecular weight heparin
    • Patients unable to take any prophylaxis are not eligible
  • HIV-positive patients with no prior AIDS-defining conditions must not be on current treatment with zidovudine (AZT)

    • Patients receiving antiretroviral therapy other than AZT are eligible
  • Not receiving any other agent which would be considered as a treatment for the lymphoma
  • Prior use of rituximab is allowed
  • Not receiving erythroid-stimulating agents (EPO: Procrit, Aranesp); use of erythroid-stimulating agents is not allowed during the study treatment
  • No prior treatment with bendamustine hydrochloride
  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: NCT01429025

Locations
United States, Iowa
Mercy Cancer Center-West Lakes Recruiting
Clive, Iowa, United States, 50325
Contact: Robert Behrens    888-244-6061      
Principal Investigator: Robert Behrens         
Medical Oncology and Hematology Associates-West Des Moines Recruiting
Clive, Iowa, United States, 50325
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Iowa Oncology Research Association CCOP Recruiting
Des Moines, Iowa, United States, 50309
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Iowa Lutheran Hospital Recruiting
Des Moines, Iowa, United States, 50316
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Mercy Medical Center - Des Moines Recruiting
Des Moines, Iowa, United States, 50314
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Medical Oncology and Hematology Associates Recruiting
Des Moines, Iowa, United States, 50314
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Medical Oncology and Hematology Associates-Des Moines Recruiting
Des Moines, Iowa, United States, 50309
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Iowa Methodist Medical Center Recruiting
Des Moines, Iowa, United States, 50309
Contact: Robert J. Behrens    610-402-2273      
Principal Investigator: Robert J. Behrens         
Siouxland Hematology-Oncology Recruiting
Sioux City, Iowa, United States, 51101-1733
Contact: Donald Bruce Wender, MD, PhD    712-252-0088    shoa@pionet.net   
Principal Investigator: Donald Wender         
St. Luke's Regional Medical Center Recruiting
Sioux City, Iowa, United States, 51104
Contact: Donald B. Wender, MD, PhD    712-252-0088      
Principal Investigator: Donald Wender         
Mercy Medical Center-Sioux City Recruiting
Sioux City, Iowa, United States, 51104
Contact: Donald B. Wender    610-402-2273      
Principal Investigator: Donald B. Wender         
Mercy Medical Center-West Lakes Recruiting
West Des Moines, Iowa, United States, 50266
Contact: Robert Behrens    888-244-6061      
Principal Investigator: Robert Behrens         
Methodist West Hospital Recruiting
West Des Moines, Iowa, United States, 50266-7700
Contact: Robert J. Behrens    515-343-1000      
Principal Investigator: Behrens Robert         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Grzegorz Nowakowski    507-538-7623      
Principal Investigator: Grzegorz Nowakowski         
United States, North Dakota
Saint Alexius Medical Center Recruiting
Bismarck, North Dakota, United States, 58501
Contact: John Reynolds    701-323-5760      
Principal Investigator: John Reynolds         
Mid Dakota Clinic Recruiting
Bismarck, North Dakota, United States, 58501
Contact: John Reynolds    701-323-5760      
Principal Investigator: John Reynolds         
Sanford Bismarck Medical Center Recruiting
Bismarck, North Dakota, United States, 58501
Contact: John Reynolds    701-323-5760      
Principal Investigator: John Reynolds         
Sponsors and Collaborators
North Central Cancer Treatment Group
Celgene Corporation
Investigators
Principal Investigator: Grzegorz S. Nowakowski, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier: NCT01429025     History of Changes
Other Study ID Numbers: N1088, NCCTG-N1088, CDR0000710726, NCI-2011-03535
Study First Received: September 2, 2011
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
Waldenström macroglobulinemia
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Rituximab
Lenalidomide
Nitrogen Mustard Compounds
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014