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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00006721
First received: December 6, 2000
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: tositumomab and iodine I 131 tositumomab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Progression-free Survival at 2 Years [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

  • Progression-free Survival at 5 Years [ Time Frame: 0-5 years ] [ Designated as safety issue: No ]
    Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

  • Overall Survival at 2 Years [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause

  • Overall Survival at 5 Years [ Time Frame: 0-5 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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


Enrollment: 571
Study Start Date: March 2001
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: doxorubicin hydrochloride
Given IV
Drug: prednisone
Given orally
Drug: vincristine sulfate
Given IV
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
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: prednisone
Given orally
Drug: vincristine sulfate
Given IV
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
Drug: doxorubicin hydrochloride
Given IV
Drug: prednisone
Given orally
Drug: vincristine sulfate
Given IV
Radiation: tositumomab and iodine I 131 tositumomab
Given IV

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT00006721

  Show 259 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Investigators
Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Research Center
Study Chair: Myron S. Czuczman, MD Roswell Park Cancer Institute
Study Chair: Sandra J. Horning, MD Stanford University
  More Information

Additional Information:
No publications provided by Southwest Oncology Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00006721     History of Changes
Other Study ID Numbers: CDR0000068321, U10CA032102, S0016, CALGB-50102, S0016
Study First Received: December 6, 2000
Results First Received: November 2, 2012
Last Updated: February 21, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
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:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Iodine-131 anti-B1 antibody
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on October 21, 2014