Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01286272
First received: January 27, 2011
Last updated: October 23, 2014
Last verified: October 2014
  Purpose

This randomized phase II trial studies how well ofatumumab and bendamustine hydrochloride with or without bortezomib works in treating patients with untreated follicular non-Hodgkin lymphoma. Monoclonal antibodies, such as ofatumumab, may block cancer growth in different ways by targeting certain cells. 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. It is not yet known whether ofatumumab and bendamustine hydrochloride are more effective with bortezomib in treating patients with follicular non-Hodgkin lymphoma.


Condition Intervention Phase
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
Biological: ofatumumab
Drug: bendamustine hydrochloride
Drug: bortezomib
Other: laboratory biomarker analysis
Procedure: positron emission tomography with radiolabeled targeting agents
Radiation: fludeoxyglucose F 18
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC # 681239) and Bendamustine in Patients With Untreated Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • CR rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PFS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves of PFS and overall survival (OS) will be generated for the two arms. The p-values of the log-rank test will be calculated to compare PFS and OS between the two arms.

  • Grade 3 or higher toxicities assessed according to NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    The toxicity profile of the two arms will be summarized using frequency tables. The chi-squared test will be conducted to compare the toxicity rate of grade 3 or higher between the two arms.

  • Pre-treatment single nucleotide polymorphisms (SNP) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The PFS will be compared among the three genotype groups of each SNP using the log-rank tests. A maxtype test will be used by taking the maximum value of the log-rank tests under dominant, recessive, and proportional hazard model. The critical value (or p-value) of the max test will be obtained by a permutation method. No multiple testing adjustment may be applied because of the small sample size.

  • Immunohistochemical (IHC) markers [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The IHC markers will be correlated with response (using the two-sample t-test) and PFS (using the Cox regression method) data. No multiple testing adjustment will be applied because of the small sample size.

  • Predictive value of FDG-PET [ Time Frame: Baseline and at 70 days ] [ Designated as safety issue: No ]
    The ratio will be correlated with response (using the two-sample t-test) and PFS (using the Cox regression method) data.


Estimated Enrollment: 130
Study Start Date: April 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (ofatumumab, bendamustine hydrochloride)

INDUCTION: Patients receive ofatumumab 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.

Biological: ofatumumab
Given IV
Other Names:
  • Arzerra
  • HuMax-CD20
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda
Other: laboratory biomarker analysis
Correlative studies
Procedure: positron emission tomography with radiolabeled targeting agents
Undergo FDG-PET
Other Name: PET with radiolabeled targeting agents
Radiation: fludeoxyglucose F 18
Undergo FDG-PET
Other Names:
  • 18FDG
  • FDG
Experimental: Arm B (ofatumumab, bendamustine hydrochloride, bortezomib)

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.

Biological: ofatumumab
Given IV
Other Names:
  • Arzerra
  • HuMax-CD20
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies
Procedure: positron emission tomography with radiolabeled targeting agents
Undergo FDG-PET
Other Name: PET with radiolabeled targeting agents
Radiation: fludeoxyglucose F 18
Undergo FDG-PET
Other Names:
  • 18FDG
  • FDG

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed follicular non-Hodgkin lymphoma, World Health Organization (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
    • Failure to submit pathology within 60 days of patient registration will be considered a major protocol violation
  • Patients must have at least one of the following indicators of poor risk disease:

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

      • Age > 60 years
      • Involvement of > 4 nodal sites
      • Stage III-IV disease
      • Hemoglobin < 12.0 g/dL
      • Lactate dehydrogenase (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; 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; 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/ul; 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/uL
  • Platelet count >= 75,000/uL
  • Creatinine =< 2.0 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limits of normal (ULN)
  • Bilirubin =< 2 x ULN
  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: NCT01286272

  Show 76 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Kristie Blum Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01286272     History of Changes
Other Study ID Numbers: NCI-2011-02625, NCI-2011-02625, CDR0000694298, CALGB 50904, CALGB-50904, U10CA180821, U10CA031946
Study First Received: January 27, 2011
Last Updated: October 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Bortezomib
Fluorodeoxyglucose F18
Nitrogen Mustard Compounds
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Diagnostic Uses of Chemicals
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiopharmaceuticals
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014