Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma
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| ClinicalTrials.gov Identifier: NCT01286272 |
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Recruitment Status :
Active, not recruiting
First Posted : January 31, 2011
Results First Posted : January 10, 2019
Last Update Posted : January 31, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ann Arbor Stage III Grade 1 Follicular Lymphoma Ann Arbor Stage III Grade 2 Follicular Lymphoma Ann Arbor Stage III Grade 3 Follicular Lymphoma Ann Arbor Stage IV Grade 1 Follicular Lymphoma Ann Arbor Stage IV Grade 2 Follicular Lymphoma Ann Arbor Stage IV Grade 3 Follicular Lymphoma Grade 3a Follicular Lymphoma | Drug: Bendamustine Hydrochloride Drug: Bortezomib Radiation: Fludeoxyglucose F-18 Other: Laboratory Biomarker Analysis Biological: Ofatumumab Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent | Phase 2 |
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 135 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | April 8, 2011 |
| Actual Primary Completion Date : | May 24, 2017 |
| Arm | Intervention/treatment |
|---|---|
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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. |
Drug: Bendamustine Hydrochloride
Given IV
Other Names:
Radiation: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: Ofatumumab Given IV
Other Names:
Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent Undergo FDG-PET
Other Name: Positron Emission Tomography with Radiolabeled Targeting Agents |
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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 or SC 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 or SC on days 1, 8, 15, and 22. Treatment repeats every 56 days for up to 4 courses. |
Drug: Bendamustine Hydrochloride
Given IV
Other Names:
Drug: Bortezomib Given IV or SC
Other Names:
Radiation: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: Ofatumumab Given IV
Other Names:
Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent Undergo FDG-PET
Other Name: Positron Emission Tomography with Radiolabeled Targeting Agents |
- Complete Response Rate [ Time Frame: From date of randomization until patient stops treatment for any reason, up to 484 days post-randomization ]
A complete response was defined using International Harmonization Project Response Criteria as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.
The complete response (CR) rate was calculated 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).
The complete response rate was calculated as the number of patients with a complete response divided by the number of patients eligible for evaluation.
- Progression-free Survival (PFS) [ Time Frame: Up to 4 years ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS rates (percentages) at 1, 2, ,3 and 4 years are defined as the percentage of patients who are alive and progression-free at the respective time points. The p-values of the log-rank test will be calculated to compare PFS between the two arms.
- The Number of Patients Who Experienced Grade 3+ Hematologic and Non-hematologic Adverse Events at Least Possibly Related to Treatment [ Time Frame: From date of randomization until patient stops treatment for any reason, up to 484 days post-randomization ]The number of patients who experienced grade 3+ hematologic and non-hematologic adverse events at least possibly related to treatment assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
- Pre-treatment Single Nucleotide Polymorphisms (SNP) [ Time Frame: Up to 10 years ]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 ]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 Fludeoxyglucose-positron-emission Tomography [ Time Frame: Up to 36-38 weeks (6-8 weeks after course 6, day 1 after last course of induction chemotherapy) ]The ratio will be correlated with response (using the two-sample t-test) and PFS (using the Cox regression method) data.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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
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Follicular Lymphoma International Prognostic Index (FLIPI score):
- Age > 60 years
- Involvement of > 4 nodal sites
- Stage III-IV disease
- Hemoglobin < 12.0 g/dL
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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)
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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 within 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 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01286272
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| Principal Investigator: | Kristie A Blum | Alliance for Clinical Trials in Oncology |
Documents provided by National Cancer Institute (NCI):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01286272 |
| Other Study ID Numbers: |
NCI-2011-02625 NCI-2011-02625 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CALGB-50904 CDR0000694298 CALGB-50904 ( Other Identifier: Alliance for Clinical Trials in Oncology ) CALGB-50904 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 31, 2011 Key Record Dates |
| Results First Posted: | January 10, 2019 |
| Last Update Posted: | January 31, 2023 |
| Last Verified: | January 2023 |
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Lymphoma Lymphoma, Follicular Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Deoxyglucose Bortezomib Bendamustine Hydrochloride Ofatumumab |
Fluorodeoxyglucose F18 Antibodies, Monoclonal Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Radiopharmaceuticals Antimetabolites Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs |