SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma

NCT00004031 | Completed Phase 3 Results DMC

• 3 other identifiers: CDR0000065658S9704U10CA032102
• Study Type: interventional
• Target: 397
• Locations: 2 countries
• Sites: 15

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and radiation and kill more cancer cells. It is not yet known whether chemoradiotherapy plus peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying chemoradiotherapy and peripheral stem cell transplantation to see how well they work compared to combination chemotherapy in treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

stage III grade 3 follicular lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult Burkitt lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II grade 3 follicular lymphoma; contiguous stage II adult diffuse small cleaved cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult Burkitt lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult Burkitt lymphoma

Outcome Measures

Primary Outcomes (2)

• 2-year Overall Survival Rates

  Percentage of participants surviving 2 years post registration

  up to 2 years post registration

• 2 Year Progression-free Survival

  Percentage of participants without disease progression up to 2 years post-registration.

  From registration until death

Secondary Outcomes (1)

• Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

  Duration of treatment and follow up until death or 3 years post registration

Study Arms (2)

CHOP/CHOP-R x 3

ACTIVE COMPARATOR

Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 8 cycles

Biological: rituximab; Drug: CHOP regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Procedure: bone marrow ablation with stem cell support

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant

EXPERIMENTAL

Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 6 cycles followed by autologous stem cell transplant.

Biological: rituximab; Drug: CHOP regimen; Drug: carmustine; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: vincristine sulfate; Procedure: bone marrow ablation with stem cell support; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

rituximab BIOLOGICAL

375 mg/m2 IV every 21 days

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

CHOP regimen DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

carmustine DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant

cyclophosphamide DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

doxorubicin hydrochloride DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

etoposide DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant

prednisone DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

vincristine sulfate DRUG

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

bone marrow ablation with stem cell support PROCEDURE

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant; CHOP/CHOP-R x 3

peripheral blood stem cell transplantation PROCEDURE

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant

radiation therapy RADIATION

CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically proven intermediate- or high-grade non-Hodgkin's lymphoma * Ann Arbor classification of "bulky" stage II, III, or IV * Must be classified as high-intermediate or high-risk according to International Age Adjusted Index * Bidimensionally measurable disease * No lymphoblastic, transformed, or mantle cell lymphomas * No CNS involvement by lymphoma * CD20 status confirmed by immunocytochemistry or flow cytometry * Must have either bilateral or unilateral bone marrow aspiration and biopsy ≥ 42 days before first course of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy (or CHOP plus rituximab \[CHOP-R\] for CD20+ disease) OR within 42 days prior to registration if CHOP/CHOP-R therapy has not begun * Must have bilateral bone marrow aspiration and biopsy within 28 days of randomization * Bone marrow involvement with lymphoma is allowed, provided there is an improvement of at least 50% if used as an evaluable site of disease * No prior lymphoma, Hodgkin's lymphoma, myelodysplastic syndromes, or leukemia NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age: * 15 to 65 Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * No nonlymphoma-related hepatic dysfunction Renal: * Creatinine no greater than 2 times ULN * Creatinine clearance at least 60 mL/min * No nonlymphoma-related renal dysfunction * No history of grade 3 hemorrhagic cystitis due to cyclophosphamide Cardiovascular: * No coronary artery disease, cardiomyopathy, congestive heart failure, or dysrhythmia requiring therapy * MUGA scan or 2-D echocardiogram required if patient's history is questionable * Ejection fraction normal Pulmonary: * DLCO or FEV\_1 at least 60% of predicted Other: * Not pregnant or nursing * Fertile patients must use effective contraception * HIV negative * No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No allergy to etoposide * No active bacterial, fungal, or viral infection PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior monoclonal antibody therapy for lymphoma except if included in a single course of CHOP/CHOP-R Chemotherapy: * No prior chemotherapy for lymphoma except for a single course of CHOP/CHOP-R\* NOTE: \*Prednisone or other corticosteroids not considered prior chemotherapy Endocrine therapy: * See Chemotherapy * Prior corticosteroids allowed Radiotherapy: * No prior radiotherapy for lymphoma * No prior thoracic radiotherapy or radiotherapy greater than 2,000 cGy to any other site Surgery: * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator
• Cancer and Leukemia Group B: collaborator
• Eastern Cooperative Oncology Group: collaborator
• NCIC Clinical Trials Group: collaborator

Study Sites (15)

Oregon Health & Science University

Portland, Oregon, 97201, United States

Location

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Doctor H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

Odette Cancer Centre at Sunnybrook

Toronto, Ontario, M4N 3M5, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

Hopital Du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Hopital du Saint-Sacrement - Quebec

Québec, Quebec, G1S 4L8, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (3)

• Stiff PJ, Unger JM, Cook J, et al.: Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). [Abstract] J Clin Oncol 29 (Suppl 15): A-8001, 2011.

  RESULT

• Cook JR, Goldman B, Tubbs RR, Rimsza L, Leblanc M, Stiff P, Fisher R. Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study. Am J Surg Pathol. 2014 Apr;38(4):494-501. doi: 10.1097/PAS.0000000000000147.

  PMID: 24625415 DERIVED

• Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. doi: 10.1056/NEJMoa1301077.

  PMID: 24171516 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Burkitt Lymphoma

Interventions

Rituximab; VAP-cyclo protocol; Carmustine; Cyclophosphamide; Doxorubicin; Etoposide; Prednisone; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Study Statistician
• Organization: SWOG Statistics and Data Management Center

2066674623

Study Officials

• Patrick J. Stiff, MD

  Loyola University

  STUDY CHAIR

• Thomas C. Shea, MD

  UNC Lineberger Comprehensive Cancer Center

  STUDY CHAIR

• David P. Schenkein, MD

  Tufts Medical Center Cancer Center

  STUDY CHAIR

• Stephen Couban, MD

  Cancer Care Nova Scotia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 1999
• First Posted: January 27, 2003
• Study Start: July 1, 1997
• Primary Completion: June 1, 2008
• Study Completion: October 31, 2013
• Last Updated: February 2, 2021
• Results First Posted: February 2, 2021

Record last verified: 2021-01

Locations

US (1); CA (14)