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

• 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: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI); Cancer and Leukemia Group B; Eastern Cooperative Oncology Group
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: December 6, 2000
• First Posted Date: January 27, 2003
• Results First Submitted Date: November 2, 2012
• Results First Posted Date: February 26, 2013
• Last Update Posted Date: September 26, 2023
• Study Start Date: March 2001
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2013)

• 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
• 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
• Overall Survival at 2 Years [ Time Frame: 0-2 years ]
  Measured from date of registration to date of death due to any cause
• Overall Survival at 5 Years [ Time Frame: 0-5 years ]
  Measured from date of registration to date of death due to any cause

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: January 22, 2013)

• 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.
• 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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• 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
• Radiation: tositumomab
  Given IV

Study Arms

• 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)

  Interventions:

  • Drug: cyclophosphamide
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
• 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.
  Interventions:

  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
• 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.
  Interventions:

  • Drug: cyclophosphamide
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
  • Radiation: tositumomab

Publications *

• Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. doi: 10.1200/JCO.2017.74.5083. Epub 2018 Jan 22.
• Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. doi: 10.1200/JCO.2012.42.4101. Epub 2012 Dec 10.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 22, 2013): 571
• Original Enrollment: Not Provided
• Estimated Study Completion Date: March 2024
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: https://swog.org/Visitors/Download/Policies/Policy43.pdf

• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Not Provided
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Cancer and Leukemia Group B
• Eastern Cooperative Oncology Group

Investigators

• 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

• PRS Account: SWOG Cancer Research Network
• Verification Date: September 2023