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

Lymphoma Clinical Trial

Official title:

SWOG-9704 A Randomized Phase III Trial Comparing Early High Dose Chemoradiotherapy and an Autologous Stem Cell Transplant to Conventional Dose CHOP Chemotherapy Plus Rituximab for CD20+ B Cell Lymphomas (With Possible Late Autologous Stem Cell Transplant) for Patients With Diffuse Aggressive Non-Hodgkin's Lymphoma in the High-Intermediate and High Risk International Classification Prognostic Groups

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004031
• Other study ID #: CDR0000065658
• Secondary ID: S9704U10CA032102
• Status: Completed
• Phase: Phase 3
• Start date: July 1997
• Est. completion date: October 31, 2013

Study information

• Verified date: January 2021
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

• Compare the overall survival and progression-free survival of patients with intermediate- or high-grade non-Hodgkin's lymphoma treated with high-dose chemoradiotherapy and autologous peripheral blood stem cell transplantation (APBSCT) vs conventional dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (or CHOP plus rituximab for CD20+ disease) with possible late APBSCT.

• Compare the toxic effects of these regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to disease risk (intermediate-high vs high).

Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients with CD20-positive disease also receive rituximab IV on day 1 (or day 0 during course 1 only). Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Within 35 days of completing the fifth course, patients with partial or complete response are randomized to one of two treatment arms.

• Arm I: Patients receive CHOP (or CHOP plus rituximab [CHOP-R]) as above. Treatment repeats every 3 weeks for 3 additional courses. After completion of chemotherapy, patients are encouraged to undergo harvest of peripheral blood stem cells (PBSC) for possible use at time of relapse. After completion of 8 courses, patients receive no additional therapy until disease progression or biopsy-proven disease.

• Arm II: Patients receive one additional course of CHOP/CHOP-R followed by filgrastim (G-CSF), sargramostim (GM-CSF), or other colony-stimulating factors used singly or in combination according to center preference. PBSC are harvested and selected for CD34+ cells. Patients under age 61 receive one of two preparative regimens: a total body irradiation (TBI)-based regimen comprising irradiation administered twice daily on days -8 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2 OR carmustine IV over 2 hours on days -6 to -4 and etoposide and cyclophosphamide as in the TBI-based regimen. Patients age 61 to 65 receive the augmented regimen comprising carmustine, etoposide, and cyclophosphamide as above. Patients receive involved field radiotherapy prior to the preparative regimen only if there is biopsy-proven residual bulk disease and at the discretion of the center. PBSC are reinfused 36-48 hours after completion of cyclophosphamide. If both bone marrow and PBSC are harvested, bone marrow is reinfused on day 0 and then PBSC are reinfused either the same day or the following day.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 360 patients (at least 135 per treatment arm) will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: October 31, 2013
• Est. primary completion date: June 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• rituximab
375 mg/m2 IV every 21 days

Drug:
• CHOP regimen

• carmustine

• cyclophosphamide

• doxorubicin hydrochloride

• etoposide

• prednisone

• vincristine sulfate

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Hopital du Saint-Sacrement - Quebec	Quebec City	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Odette Cancer Centre at Sunnybrook	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (5)

Lead Sponsor	Collaborator
Southwest Oncology Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 di

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year Overall Survival Rates	Percentage of participants surviving 2 years post registration	up to 2 years post registration
Primary	2 Year Progression-free Survival	Percentage of participants without disease progression up to 2 years post-registration.	From registration until death
Secondary	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Adverse Events (AEs) are reported by CTCAE Version 2.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.; Higher grades indicate higher severity of adverse events.	Duration of treatment and follow up until death or 3 years post registration