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S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in Newly Diagnosed Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00006721
Recruitment Status : Active, not recruiting
First Posted : January 27, 2003
Results First Posted : February 26, 2013
Last Update Posted : September 26, 2023
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
SWOG Cancer Research Network

Study Description
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Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Radiation: tositumomab Phase 3

Detailed Description:

OBJECTIVES:

  • Compare the progression-free survival and overall survival of patients with newly diagnosed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without either rituximab or iodine I 131 tositumomab (monoclonal antibody anti-B1). (CHOP chemotherapy alone arm closed to accrual as of 12/15/02)
  • Compare the response rate of these patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.
  • Compare the molecular remission rates of this patient population treated with these regimens.
  • Determine the incidence and time to development of human anti-mouse antibody positivity.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to whether microglobulin is greater than upper limit of normal (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm I closed to accrual as of 12/15/02)

  • Arm I (CHOP only): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
  • Arm II (CHOP + rituximab): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
  • Arm III (CHOP + tositumomab): Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.

Patients are followed on day 200, at 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 500 patients (250 per treatment arm) will be accrued for this study within 5.5 years. (Arm I closed to accrual as of 12/15/02)

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 571 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Trial of CHOP Plus Rituximab vs CHOP Plus Iodine-131-Labeled Monoclonal Anti-B1 Antibody (Tositumomab) for Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas
Study Start Date : March 2001
Actual Primary Completion Date : September 2011
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm I (CHOP only)

Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day

1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)

 Drug: cyclophosphamide
Given IV
Other Name: cytoxan

Drug: doxorubicin
Given IV
Other Name: adriamycin

Drug: prednisone
Given orally
Other Name: steroid

Drug: vincristine
Given IV
Other Name: oncovin
Experimental: Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
 Biological: rituximab
Given IV
Other Name: rituxan

Drug: cyclophosphamide
Given IV
Other Name: cytoxan

Drug: doxorubicin
Given IV
Other Name: adriamycin

Drug: prednisone
Given orally
Other Name: steroid

Drug: vincristine
Given IV
Other Name: oncovin
Experimental: Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
 Drug: cyclophosphamide
Given IV
Other Name: cytoxan

Drug: doxorubicin
Given IV
Other Name: adriamycin

Drug: prednisone
Given orally
Other Name: steroid

Drug: vincristine
Given IV
Other Name: oncovin

Radiation: tositumomab
Given IV


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free Survival at 2 Years [ Time Frame: 0-2 years ]
    Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

  2. Progression-free Survival at 5 Years [ Time Frame: 0-5 years ]
    Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

  3. Overall Survival at 2 Years [ Time Frame: 0-2 years ]
    Measured from date of registration to date of death due to any cause

  4. Overall Survival at 5 Years [ Time Frame: 0-5 years ]
    Measured from date of registration to date of death due to any cause


Secondary Outcome Measures :
  1. Objective Response (Confirmed and Unconfirmed Complete and Partial Responses) [ Time Frame: Assessed 200 days and 365 days after initiation of therapy and then every 6 months until death ]
    Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

  2. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events at end of cycle 1-6 of CHOP or R-CHOP, the end of cycle 1-6 of CHOP and once 2 weeks after the completion of I-131 treatment. For either arm, once 3 months after removal from protocol treatment ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma

    • Grade I-III disease
  • Cluster of differentiation antigen 20 (CD20) antigen positive
  • Fewer than 5,000/mm^3 circulating lymphoid cells on a white blood cell (WBC) differential count
  • Bidimensionally measurable disease
  • Bone marrow aspiration and biopsy within the past 42 days
  • No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • Granulocyte count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • Not specified

Renal:

  • Not specified

Cardiovascular:

  • No impaired cardiac status, including:

    • Severe coronary artery disease
    • Cardiomyopathy
    • Congestive heart failure
    • Serious arrhythmia
  • Ejection fraction at least lower limit of normal by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram for questionable cardiac history

Other:

  • No hypersensitivity to iodine
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • HIV negative
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior monoclonal antibodies for cancer

Chemotherapy:

  • No prior chemotherapy for lymphoma

    • Prior prednisone for non-lymphoma related illnesses allowed

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy for lymphoma

Surgery:

  • See Disease Characteristics
Contacts and Locations
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Information from the National Library of Medicine

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): NCT00006721


Locations
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Sponsors and Collaborators
SWOG Cancer Research Network
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Investigators
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Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Center
Study Chair: Myron S. Czuczman, MD Roswell Park Cancer Institute
Study Chair: Sandra J. Horning, MD Stanford University
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: SWOG Cancer Research Network
ClinicalTrials.gov Identifier: NCT00006721    
Other Study ID Numbers: CDR0000068321
U10CA032102 ( U.S. NIH Grant/Contract )
S0016 ( Other Identifier: SWOG )
CALGB-50102 ( Other Identifier: CALGB )
S0016 ( Other Identifier: ECOG )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: February 26, 2013
Last Update Posted: September 26, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://swog.org/Visitors/Download/Policies/Policy43.pdf

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SWOG Cancer Research Network:
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
 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
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones