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Clinical Trials (PDQ®)

Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, Supportive care, TreatmentActive18 and overNCI, OtherCDR0000683312
E2408, NCI-2011-02644, ECOG-E2408, NCT01216683

Trial Description

Summary

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

PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.

Further Study Information

OBJECTIVES:

Primary

  • To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib.
  • To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide.

Secondary

  • To determine the 3-year progression-free survival and the 5-year overall survival of these patients.
  • To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life.
  • To examine the association between baseline FLIPI information and outcome of these patients.
  • To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome.
  • To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory)

OUTLINE: Patients are stratified according to FLIPI-1score (1 or 2 vs 3 vs 4 or 5) and GELF tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

  • Arm II: Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm I.

  • Arm III: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy.

Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository.

After completion of study therapy, patients are followed up periodically for 15 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology
  • Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., ≥ 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology
  • Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy) required if the interval since tissue diagnosis of low-grade malignant lymphoma is > 24 months
  • Bone marrow biopsy alone not acceptable
  • Stage II, III, or IV AND grade 1, 2, or 3a disease
  • Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:
  • Patient must meet ≥ 1 of the following GELF criteria:
  • Nodal or extranodal mass ≥ 7 cm
  • At least 3 nodal masses > 3.0 cm in diameter
  • Systemic symptoms due to lymphoma or B symptoms
  • Splenomegaly with spleen > 16 cm by CT scan
  • Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
  • Leukemic presentation (≥ 5.0 x 10^9/L malignant circulating follicular cells)
  • Cytopenias (polymorphonuclear leukocytes < 1.0 X 10^9/L, hemoglobin < 10 g/dL, and/or platelets < 100 x 10^9/L)
  • Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):
  • Age ≥ 60 years
  • Stage III-IV disease
  • Hemoglobin level < 12 g/dL
  • > 4 nodal areas
  • Serum LDH level above normal
  • At least 1 objective measurable disease parameter
  • Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization
  • Measurable disease in the liver is required if the liver is the only site of lymphoma

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm³ (includes neutrophils and bands)
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 2.0 mg/dL
  • AST and ALT ≤ 5 x upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 x ULN
  • Total bilirubin ≤ 1.5 x ULN (patients with known Gilbert disease should contact the study PI)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 effective methods (1 highly effective and 1 additional effective method) of contraception ≥ 28 days before, during, and for ≥ 28 days after completing study treatment
  • HIV-positive patients must meet all of the following criteria:
  • HIV is sensitive to antiretroviral therapy
  • Must be willing to take effective antiretroviral therapy if indicated
  • No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis
  • 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 ≥ 2 months following completion of study therapy or until the CD4 cells recover to over 250 cells/mm³
  • No recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for ≥ 2 years
  • No active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
  • No ≥ grade 2 neuropathy
  • No myocardial infarction within the past 6 months
  • No NYHA class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • No serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • No known hypersensitivity to boron or mannitol
  • No chronic carriers of hepatitis B virus (HBV) with positive hepatitis surface antigen (HBsAg +)
  • Patients with a prior history of HBV infection, but immune, with only IgG hepatitis core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine 100 mg po daily) for ≥ 1 week prior to course 1 and throughout induction and continuation therapy and for ≥ 12 months after the last rituximab dose
  • Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® (for patients randomized to arm III)

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma
  • Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy
  • A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

National Cancer Institute

Andrew M. EvensPrincipal Investigator

Trial Sites

U.S.A.
California
  Greenbrae
 Marin Cancer Institute at Marin General Hospital
 Peter D. Eisenberg Ph: 415-925-5000
  Email: info@marinspecialtycare.com
Illinois
  Centralia
 Centralia Oncology Clinic
 James L. Wade Ph: 217-876-4740
  Email: kcheek@dmhhs.org
  Decatur
 Cancer Care Center of Decatur
 James L. Wade Ph: 217-876-4740
  Email: kcheek@dmhhs.org
 Decatur Memorial Hospital Cancer Care Institute
 James L. Wade Ph: 217-876-4740
  Email: kcheek@dmhhs.org
  Effingham
 Crossroads Cancer Center
 James L. Wade Ph: 217-876-4740
  Email: kcheek@dmhhs.org
  Rockford
 Advanced Care and Treatment Medical Group, PC
 Harvey Eric Einhorn Ph: 779-696-9400
  Email: cancercare@swedishamerican.org
Iowa
  Ames
 McFarland Clinic, PC
 Joseph James Merchant Ph: 515-239-2621
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Jon E Arnason
  Email: jarnason@bidmc.harvard.edu
Michigan
  Pontiac
 St. Joseph Mercy Oakland
 Christopher M Reynolds Ph: 734-712-4673
Minnesota
  Bemidji
 MeritCare Bemidji
 Preston D. Steen Ph: 701-234-6161
  Brainerd
 St. Joseph's Medical Center
 Bret E Friday Ph: 888-203-7267
  Duluth
 CCOP - Duluth
 Bret E Friday Ph: 888-203-7267
 Essentia Health - Duluth Clinic
 Bret E Friday Ph: 888-203-7267
 Miller - Dwan Medical Center
 Bret E Friday Ph: 888-203-7267
  Rochester
 Mayo Clinic Cancer Center
 Thomas M. Habermann Ph: 507-538-7623
Missouri
  Cape Girardeau
 Saint Francis Medical Center
 James L. Wade Ph: 217-876-4740
  Email: kcheek@dmhhs.org
New Jersey
  New Brunswick
 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
 Kevin A David Ph: 732-235-8675
North Dakota
  Fargo
 Roger Maris Cancer Center at MeritCare Hospital
 Preston D. Steen Ph: 701-234-6161
 Preston D. Steen Ph: 701-234-6161
 Sanford Clinic North-Fargo
 Preston D. Steen Ph: 701-234-6161
Ohio
  Canton
 Aultman Cancer Center at Aultman Hospital
 Kisa E Weeman Ph: 330-363-6891
 Mercy Cancer Center at Mercy Medical Center
 Mitchell Haut Ph: 888-293-4673
  Chardon
 Geauga Regional Hospital
 Paolo F Caimi Ph: 800-641-2422
  Cleveland
 Case Comprehensive Cancer Center
 Paolo F Caimi Ph: 800-641-2422
 Cleveland Clinic Taussig Cancer Center
 Paolo F Caimi Ph: 800-641-2422
  Mayfield Heights
 University Hospitals Ireland Cancer Center at Landerbrook Health Center
 Paolo F Caimi Ph: 800-641-2422
  Mentor
 Lake/University Ireland Cancer Center
 Paolo F Caimi Ph: 800-641-2422
  Middleburg Heights
 Southwest General Health Center
 Paolo F Caimi Ph: 800-641-2422
  Orange Village
 UHHS Chagrin Highlands Medical Center
 Paolo F Caimi Ph: 800-641-2422
  Sandusky
 University Hospitals Ireland Cancer Center at Firelands Regional Medical Center
 Paolo F Caimi Ph: 800-641-2422
  Wadsworth
 University Hospitals Sharon Health Center
 Paolo F Caimi Ph: 800-641-2422
  Westlake
 UHHS Westlake Medical Center
 Paolo F Caimi Ph: 800-641-2422
 UH-Seidman Cancer Center at Saint John Medical Center
 Paolo F Caimi Ph: 800-641-2422
Pennsylvania
  Abington
 Rosenfeld Cancer Center at Abington Memorial Hospital
 Willard G. Andrews Ph: 215-481-2402
  Bryn Mawr
 Bryn Mawr Hospital
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
  Danville
 Geisinger Cancer Institute at Geisinger Health
 Edward J Gorak Ph: 570-271-5251
  Hazleton
 Geisinger Hazleton Cancer Center
 Edward J Gorak Ph: 570-271-5251
  Lewisburg
 Geisinger Medical Oncology at Evangelical Community Hospital
 Edward J Gorak Ph: 570-271-5251
  Lewistown
 Lewistown Hospital
 Edward J Gorak Ph: 570-271-5251
  Paoli
 Cancer Center of Paoli Memorial Hospital
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
  Pottsville
 Geisinger Medical Oncology-Pottsville
 Edward J Gorak Ph: 570-271-5251
  State College
 Geisinger Medical Group - Scenery Park
 Edward J Gorak Ph: 570-271-5251
  West Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Terrence P. Cescon Ph: 610-988-9323
  Wilkes-Barre
 Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
 Edward J Gorak Ph: 570-271-5251
South Dakota
  Sioux Falls
 Sanford Cancer Center at Sanford USD Medical Center
 Preston D. Steen Ph: 701-234-6161
 Preston D. Steen Ph: 701-234-6161
Wisconsin
  Green Bay
 Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center
 Dhimant R. Patel Ph: 800-252-2990
  La Crosse
 Gundersen Lutheran Center for Cancer and Blood
 Kurt Oettel Ph: 608-775-2385
  Email: cancerctr@gundluth.org
  Marinette
 Vince Lombardi Cancer Clinic - Marinette
 Dhimant R. Patel Ph: 800-252-2990
  Oshkosh
 Vince Lombardi Cancer Clinic - Oshkosh
 Dhimant R. Patel Ph: 800-252-2990
  Sheboygan
 Vince Lombardi Cancer Clinic - Sheboygan
 Dhimant R. Patel Ph: 800-252-2990
  Summit
 Aurora Medical Center
 Dhimant R. Patel Ph: 800-252-2990
  Two Rivers
 Vince Lombardi Cancer Clinic - Two Rivers
 Dhimant R. Patel Ph: 800-252-2990

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01216683
ClinicalTrials.gov processed this data on October 20, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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