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AzTrials

LymphomaPhase 3NCT00004031

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

A Phase 3 study testing rituximab, CHOP regimen and carmustine in people with Lymphoma, run by SWOG Cancer Research Network at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 15 to 65 years
Conditions the study is for
Lymphoma
What is being tested?
rituximab, CHOP regimen and carmustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
397 participants
Where
15 sitesin 2 countries
Study dates
Jul 1997to 31 Oct 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

Canada14 sites

  • Tom Baker Cancer Centre - Calgary

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute at University of Alberta

    Edmonton, Alberta, T6G 1Z2

  • Nova Scotia Cancer Centre

    Halifax, Nova Scotia, B3H 1V7

  • Margaret and Charles Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program at London Health Sciences Centre

    London, Ontario, N6A 4L6

  • Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • Hopital Notre-Dame du CHUM

    Montreal, Quebec, H2L 4M1

  • Hopital Du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Centre Hospitalier Universitaire de Quebec

    Québec, Quebec, G1R 2J6

  • Hopital du Saint-Sacrement - Quebec

    Québec, Quebec, G1S 4L8

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

  • Doctor H. Bliss Murphy Cancer Centre

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

  • Odette Cancer Centre at Sunnybrook

    Toronto, Ontario, M4N 3M5

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United States1 site

  • Oregon Health & Science University

    Portland, Oregon, 97201

Other trials in United States

About this study

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

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.

Read the detailed 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.

Conditions
Lymphoma
Being tested
rituximab, CHOP regimen, carmustine, cyclophosphamide, doxorubicin hydrochloride
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
Medical subject headings
Lymphoma, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00004031
Study groupRoleWhat they receive
CHOP/CHOP-R x 3Active comparatorCyclophosphamide 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
Receives: 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 TransplantExperimentalCyclophosphamide 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 2-year Overall Survival Rates

    Percentage of participants surviving 2 years post registration

    Measured: up to 2 years post registration

  2. 2 Year Progression-free Survival

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

    Measured: From registration until death

Secondary outcomes (1)

  1. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJul 1997
  3. Primary completion1 Jun 2008
  4. Study completion31 Oct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004031
Sponsor's protocol ID
CDR0000065658
Other IDs
S9704, U10CA032102
Status last verified
Jan 2021
First submitted
10 Dec 1999
Last updated
2 Feb 2021
Data monitoring committee
Yes

Publications

  • 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.

  • 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.

    PubMed 24625415

  • 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.

    PubMed 24171516

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rituximab, CHOP regimen and carmustine in people with Lymphoma, run by SWOG Cancer Research Network at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year Overall Survival Rates (time frame: up to 2 years post registration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004031, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2021.

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