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A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC # 681239, IND # 58443) and Bendamustine in Patients With Untreated Follicular Lymphoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
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 I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I 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

Thank you

Trial Information

A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC # 681239, IND # 58443) and Bendamustine in Patients With Untreated Follicular Lymphoma


PRIMARY OBJECTIVES:

I. To determine the complete response (CR) rate in newly diagnosed, untreated follicular
lymphoma patients receiving 6 cycles of ofatumumab-bendamustine (ARM A) and 6 cycles of
ofatumumab, bortezomib, and bendamustine (ARM B) using International Harmonization Project
Response Criteria.

SECONDARY OBJECTIVES:

I. To determine progression-free survival (PFS) of patients with untreated follicular
lymphoma after 6 cycles of ofatumumab-bendamustine (ARM A) followed by maintenance
ofatumumab and after 6 cycles of ofatumumab, bortezomib, and bendamustine followed by
maintenance ofatumumab and bortezomib (ARM B).

II. To determine the toxicity profile of ofatumumab and bendamustine and ofatumumab,
bortezomib, and bendamustine in patients with untreated high-risk follicular lymphoma.

III. To determine if changes in both qualitative and semi-quantitative fludeoxyglucose
(FDG)-positron-emission tomography (PET) findings at baseline, after cycle 2 (day 32-35),
and at end of therapy (6-8 weeks after the last cycle of induction chemotherapy but prior to
maintenance therapy) with ofatumumab-bendamustine and ofatumumab, bortezomib, and
bendamustine correlate with response and PFS in patients with high-risk follicular lymphoma.

IV. To assess if a combinatorial approach using both qualitative and semiquantitative
changes in FDG-PET and computed tomography (CT) or magnetic resonance imaging (MRI) studies
at baseline, after cycle 2 (day 32-35), and at end of therapy (6-8 weeks after the last
cycle of induction chemotherapy prior to maintenance therapy) would result in a higher
predictive value for response and PFS in patients with high-risk follicular lymphoma.

V. To correlate all molecular parameters with FDG-PET parameters in determination of
response and PFS.

VI. To correlate pre-treatment single nucleotide polymorphisms with response and PFS
following ofatumumab-bendamustine and ofatumumab, bortezomib, and bendamustine therapy in
patients with untreated high-risk follicular lymphoma.

VII. To correlate CD-68, bcl-2, Ki-67, FOXP3, activated cytotoxic T-cells,
lymphoma-associated macrophages (LAM), MUM1, CD10, nuclear p65 and cREL subunits of NFkB,
and selected genetic translocations by fluorescent in situ hybridization (FISH) analysis
(such as Bcl-2 and Bcl-6) with response and PFS in patients receiving initial therapy for
high-risk follicular lymphoma.

VIII. To determine whether immune gene signatures previously identified as prognostic
factors in follicular lymphoma can be applied to paraffin-embedded tissues in ofatumumab and
bendamustine or ofatumumab, bendamustine, and bortezomib treated patients; evaluate microRNA
signatures associated with these gene signatures and outcome.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM A:

INDUCTION: Patients receive ofatumumab intravenously (IV) over 2-8 hours on day 1 and
bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2. Treatment repeats every 35
days for up to 6 courses. Patients without disease progression continue on to maintenance
therapy.

MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive
ofatumumab IV over 2-8 hours on day 1. Treatment repeats every 56 days for up to 4 courses.

ARM B:

INDUCTION: Patients receive ofatumumab IV over 2-8 hours on day 1, bendamustine
hydrochloride IV over 30-60 minutes on days 1 and 2, and bortezomib IV over 3-5 seconds on
days 1, 8, 15, and 22. Treatment repeats every 35 days for up to 6 courses. Patients without
disease progression continue on to maintenance therapy.

MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive
ofatumumab IV over 2-8 hours on day 1 and bortezomib IV over 3-5 seconds on days 1, 8, 15,
and 22. Treatment repeats every 56 days for up to 4 courses.

Blood and tumor tissue samples may be collected at baseline and at progression or relapse
for correlative studies. Patients also undergo FDG-PET at baseline and periodically for
restaging.

After completion of study treatment, patients are followed up every 4 months for 2 years and
then every 6 months for up to 10 years.


Inclusion Criteria:



- Histologically confirmed follicular non-Hodgkin lymphoma, WHO classification grade 1,
2, or 3a (> 15 centroblasts per high-power field with centrocytes present)

- Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they
may be submitted in conjunction with nodal biopsies

- Fine-needle aspirates are not acceptable

- Patients must have at least one of the following indicators of poor risk disease:

- >= 3 risk factors by the Follicular Lymphoma International Prognostic Index
(FLIPI score), or 2 risk factors by the FLIPI and at least one bulky mass or
lymph node > 6 cm in size;

- FLIPI score:

- Age > 60 years

- Involvement of > 4 nodal sites

- Stage III-IV disease

- Hemoglobin < 12.0 mg/dL

- LDH > Upper limit of normal (ULN)

- 0-1 of the above risk factors: Low Risk

- 2 risk factors: Intermediate Risk

- >= 3 risk factors: Poor Risk

- No prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or radioimmunotherapy

- No corticosteroids are permitted, except for maintenance therapy for a non malignant
disease or to prevent treatment-related ofatumumab reactions (maintenance therapy
dose must not exceed 20 mg/day prednisone or equivalent)

- Measurable disease must be present either on physical examination or imaging studies

- Non-measurable disease alone is not acceptable

- Any tumor mass > 1 cm is acceptable

- Lesions that are considered non-measurable include the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Bone marrow involvement (involvement by non-Hodgkin lymphoma should be
noted)

- Patients must have no known central nervous system (CNS) involvement by lymphoma

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Patients must be non-pregnant and non-nursing; due to the unknown teratogenic
potential of this regimen, pregnant or nursing patients may not be enrolled; women of
childbearing potential must have a negative serum or urine pregnancy test 10-14 days
prior to registration; in addition, women and men of childbearing potential must
commit to use an effective form of contraception throughout their participation in
this study due to the teratogenic potential of the therapy utilized in this trial;
appropriate methods of birth control include abstinence, oral contraceptives,
implantable hormonal contraceptives (Norplant), or double barrier method (diaphragm
plus condom)

- Patients with human immunodeficiency virus (HIV) infection are eligible; patients
with HIV infection must meet the following: no evidence of co-infection with
hepatitis B or C; CD4+ count > 400/µl; no evidence of resistant strains of HIV; on
anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL; no
history of acquired immunodeficiency syndrome (AIDS)-defining conditions; no
zidovudine or stavudine are allowed owing to overlapping toxicity with chemotherapy

- Patients must have no evidence of active hepatitis B or C infection (i.e., no
positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV]
antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface
antigen [HBsAg] +) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable at
baseline and they are closely monitored for evidence of active HBV infection by HBV
DNA testing at each treatment cycle; after completing treatment, HBsAg + patients
must be monitored by HBV DNA testing every 2 months for 6 months post-treatment,
while continuing lamivudine

- Granulocytes >= 1,000/μL

- Platelet count >= 75,000/μL

- Creatinine =< 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

- Bilirubin =< 2 x ULN

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response (CR) rate

Outcome Time Frame:

Up to 10 years

Safety Issue:

No

Principal Investigator

Kristie Blum

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02625

NCT ID:

NCT01286272

Start Date:

April 2011

Completion Date:

Related Keywords:

  • 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 I Grade 1 Follicular Lymphoma
  • Stage I Grade 2 Follicular Lymphoma
  • Stage I 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
  • Lymphoma, Non-Hodgkin

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Ingalls Memorial HospitalHarvey, Illinois  60426
North Shore University HospitalManhasset, New York  11030
Eastern Maine Medical CenterBangor, Maine  04401
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Weill Medical College of Cornell UniversityNew York, New York  10021
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Iredell Memorial HospitalStatesville, North Carolina  28677
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Altru Cancer CenterGrand Forks, North Dakota  58206
Randolph HospitalAsheboro, North Carolina  27203
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Queen's Medical CenterHonolulu, Hawaii  96813
University of North CarolinaChapel Hill, North Carolina  27599
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and HospitalHonolulu, Hawaii  96813
Virginia Commonwealth UniversityRichmond, Virginia  
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Castle Medical CenterKailua, Hawaii  96734
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Oncare Hawaii Inc-POB IIHonolulu, Hawaii  96813
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Minneapolis Veterans Medical CenterMinneapolis, Minnesota  55417
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Missouri Baptist Medical CenterSaint Louis, Missouri  63131
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Kinston Medical Specialists PAKinston, North Carolina  28501
Kettering Medical CenterKettering, Ohio  45429
Saint Charles HospitalOregon, Ohio  43616
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
University of IllinoisChicago, Illinois  60612
Moores University of California San Diego Cancer CenterLA Jolla, California  92093
Michiana Hematology Oncology-PC WestvilleWestville, Indiana  46391
University of Missouri - Ellis FischelColumbia, Missouri  65203
Moses Cone Health System-Regional Cancer CenterGreensboro, North Carolina  27403
Annie Penn Memorial HospitalReidsville, North Carolina  27320
Monter Cancer CenterLake Success, New York  11042
Kuakini Medical CenterHonolulu, Hawaii  96817
Wilcox Memorial Hospital and Kauai Medical ClinicLihue, Hawaii  96766-1099
Saint Francis HospitalGreenville, South Carolina  29601
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Michiana Hematology Oncology PC-MishawakaMishawaka, Indiana  46545-1470
Hematology Oncology Associates of Central New York PCEast Syracuse, New York  13057
Franciscan St. Francis HealthIndianapolis, Indiana  46237
Cancer and Leukemia Group BChicago, Illinois  60606
North Shore-LIJ Health System CCOPManhasset, New York  11030
Oncare Hawaii Inc - Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701