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A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete remission (CR) rate after induction therapy

Safety Issue:

No

Principal Investigator

Andrew M. Evens, DO, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

Unspecified

Study ID:

CDR0000683312

NCT ID:

NCT01216683

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • Lymphoma
  • Lymphoma, Follicular

Name

Location

Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
CCOP - Carle Cancer Center Urbana, Illinois  61801
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Veterans Affairs Medical Center - East Orange East Orange, New Jersey  07018-1095
Aurora Presbyterian Hospital Aurora, Colorado  80012
Boulder Community Hospital Boulder, Colorado  80301-9019
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
CCOP - Colorado Cancer Research Program Denver, Colorado  80224-2522
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United Hospital Longmont, Colorado  80502
St. Mary - Corwin Regional Medical Center Pueblo, Colorado  81004
North Suburban Medical Center Thornton, Colorado  80229
Rush-Copley Cancer Care Center Aurora, Illinois  60507
Hinsdale Hematology Oncology Associates Hinsdale, Illinois  60521
Saint Anthony Memorial Health Centers Michigan City, Indiana  46360
Mercy Medical Center - Sioux City Sioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
St. Luke's Regional Medical Center Sioux City, Iowa  51104
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
MeritCare Bemidji Bemidji, Minnesota  56601
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - Duluth Duluth, Minnesota  55805-1983
CCOP - Duluth Duluth, Minnesota  55805
Miller - Dwan Medical Center Duluth, Minnesota  55805
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
CCOP - MeritCare Hospital Fargo, North Dakota  58122
Aultman Cancer Center at Aultman Hospital Canton, Ohio  44710-1799
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center Cleveland, Ohio  44109
Geisinger Medical Group - Scenery Park State College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Dean Medical Center - Madison Madison, Wisconsin  53717
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
Marshfield Clinic - Indianhead Center Rice Lake, Wisconsin  54868
Methodist Medical Center of Illinois Peoria, Illinois  61636
Rush University Medical Center Chicago, Illinois  60612-3824
UMASS Memorial Cancer Center - University Campus Worcester, Massachusetts  01605-2982
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Wesley Medical Center Wichita, Kansas  67214
Bellin Memorial Hospital Green Bay, Wisconsin  54301
UMDNJ University Hospital Newark, New Jersey  07103
Cancer Institute of New Jersey at Hamilton Hamilton, New Jersey  08690
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
Waukesha Memorial Hospital Regional Cancer Center Waukesha, Wisconsin  53188
NYU Cancer Institute at New York University Medical Center New York, New York  10016
Mary Babb Randolph Cancer Center at West Virginia University Hospitals Morgantown, West Virginia  26506
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa Regional Ottumwa, Iowa  52501
Hunterdon Regional Cancer Center at Hunterdon Medical Center Flemington, New Jersey  08822
Lewistown Hospital Lewistown, Pennsylvania  17044
Mount Nittany Medical Center State College, Pennsylvania  16803
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Swedish-American Regional Cancer Center Rockford, Illinois  61104-2315
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
Dakota Cancer Institute at Dakota Clinic - South University Fargo, North Dakota  58103-4940
Geisinger Cancer Institute at Geisinger Health Danville, Pennsylvania  17822-0001
West Virginia University Health Sciences Center - Charleston Charleston, West Virginia  25302
Gundersen Lutheran Center for Cancer and Blood La Crosse, Wisconsin  54601
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Decatur Memorial Hospital Cancer Care Institute Decatur, Illinois  62526
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Marlton, New Jersey  08053
Joan Karnell Cancer Center at Pennsylvania Hospital Philadelphia, Pennsylvania  19107
Fox Valley Hematology and Oncology - East Grant Street Appleton, Wisconsin  54911-3496
Poudre Valley Hospital Fort Collins, Colorado  80524
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise, Idaho  83706
St. Joseph Medical Center Bloomington, Illinois  61701
Graham Hospital Canton, Illinois  61520
Memorial Hospital Carthage, Illinois  62321
Eureka Community Hospital Eureka, Illinois  61530
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Community Cancer Center Normal, Illinois  61761
Community Hospital of Ottawa Ottawa, Illinois  61350
Cancer Treatment Center at Pekin Hospital Pekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
OSF St. Francis Medical Center Peoria, Illinois  61637
Proctor Hospital Peoria, Illinois  61614
Illinois Valley Community Hospital Peru, Illinois  61354
St. Joseph's Medical Center Brainerd, Minnesota  56401
Wood County Oncology Center Bowling Green, Ohio  43402
Toledo Clinic - Oregon Oregon, Ohio  43616
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
Bryn Mawr Hospital Bryn Mawr, Pennsylvania  19010
Lankenau Cancer Center at Lankenau Hospital Wynnewood, Pennsylvania  19096
St. Anthony Central Hospital Denver, Colorado  80204-1335
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Stanford Cancer Center Stanford, California  94305-5824
Cancer Care and Hematology Specialists of Chicagoland - Niles Niles, Illinois  60714
McFarland Clinic, PC Ames, Iowa  50010
Lawrence Memorial Hospital Lawrence, Kansas  66044
Greater Baltimore Medical Center Cancer Center Baltimore, Maryland  21204
Willmar Cancer Center at Rice Memorial Hospital Willmar, Minnesota  56201
Summa Center for Cancer Care at Akron City Hospital Akron, Ohio  44309-2090
Geisinger Hazleton Cancer Center Hazleton, Pennsylvania  18201
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center Hershey, Pennsylvania  17033-0850
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
Hematology and Oncology Associates of Northeastern Pennsylvania Scranton, Pennsylvania  18510
Marshfield Clinic - Chippewa Center Chippewa Falls, Wisconsin  54729
Marshfield Clinic Cancer Care at Regional Cancer Center Eau Claire, Wisconsin  54701
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center Green Bay, Wisconsin  54311
UW Cancer Center Johnson Creek Johnson Creek, Wisconsin  53038
Vince Lombardi Cancer Clinic - Marinette Marinette, Wisconsin  54143
Marshfield Clinic - Lakeland Center Minocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's Hospital Rhinelander, Wisconsin  54501
Vince Lombardi Cancer Clinic - Sheboygan Sheboygan, Wisconsin  53081
Marshfield Clinic at Saint Michael's Hospital Stevens Point, Wisconsin  54481
Aurora Medical Center Summit, Wisconsin  53066
Vince Lombardi Cancer Clinic - Two Rivers Two Rivers, Wisconsin  54241
Oncology Alliance, SC - Milwaukee - West Wauwatosa, Wisconsin  53226
Marshfield Clinic - Weston Center Weston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids, Wisconsin  54494
Regional Cancer Center at Memorial Medical Center Springfield, Illinois  62781-0001
Regional Cancer Center at Oconomowoc Memorial Hospital Oconomowoc, Wisconsin  53066
University of Wisconcin Cancer Center at Aspirus Wausau Hospital Wausau, Wisconsin  54401
Galesburg Clinic, PC Galesburg, Illinois  61401
Cancer Center of Paoli Memorial Hospital Paoli, Pennsylvania  19301-1792
Minnesota Oncology - Maplewood Maplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
Lakeview Hospital Stillwater, Minnesota  55082
Minnesota Oncology - Woodbury Woodbury, Minnesota  55125
Clarian Arnett Cancer Care Lafayette, Indiana  47904
California Cancer Care, Incorporated - Greenbrae Greenbrae, California  94904
Vince Lombardi Cancer Clinic - Oshkosh Oshkosh, Wisconsin  54904
Langlade Memorial Hospital Antigo, Wisconsin  54409
Riverview UW Cancer Center at Riverview Hospital Wisconsin Rapids, Wisconsin  54494
Littleton Adventist Hospital Littleton, Colorado  80122
Parker Adventist Hospital Parker, Colorado  80138
Roger Maris Cancer Center at MeritCare Hospital Fargo, North Dakota  58122
Horizon Oncology Center Lafayette, Indiana  47905