SWOG-9400 Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Previously Untreated Acute Lymphocytic Leukemia

NCT ID: NCT00002665

Last Updated: 2015-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-07-31

Study Completion Date

2003-12-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with or without bone marrow transplantation in treating patients who have acute lymphocytic leukemia.

Detailed Description

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OBJECTIVES: I. Evaluate if front line induction therapy with daunorubicin, vincristine, prednisone, and asparaginase is sufficiently effective to warrant a phase III trial in patients with acute lymphocytic leukemia (ALL). II. Assess the toxicity of this regimen in this patient population. III. Assess disease free and overall survival and toxicity associated with allogeneic bone marrow transplantation for ALL patients in first remission following induction and consolidation therapy. IV. Assess disease free and overall survival and toxicity associated with sequential regimens of mercaptopurine, methotrexate and vincristine, doxorubicin, dexamethasone, and cyclophosphamide, thioguanine, and cytarabine in ALL patients in first remission who are ineligible for allogeneic bone marrow transplantation. V. Evaluate the prognostic significance of cell surface immunophenotype, Philadelphia chromosome, and polymerase chain reaction detected BCR/abl fusion in this patient population.

OUTLINE: Patients are stratified according to age (15 to 29 vs 30 to 49 vs 50 to 65), performance status (0-1 vs 2-3), participating center, and candidate for allogeneic bone marrow transplantation (yes vs no). Patients receive induction chemotherapy consisting of daunorubicin IV on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-28, and asparaginase IV or intramuscularly (IM) on days 15-24. Patients with persistent leukemia on day 21, receive additional induction therapy consisting of daunorubicin IV on days 22 and 23, vincristine IV on days 29 and 36, and oral prednisone continuing to day 42. Patients with CNS leukemia receive additional therapy beginning on day 1 of induction chemotherapy consisting of methotrexate intrathecally (IT) or intraventricularly twice weekly until blasts are absent in spinal fluid. Patients receive oral leucovorin calcium every 6 hours for a total of 4 doses following each IT dose in the absence of blood count recovery. Following absence of spinal fluid blasts, patients receive methotrexate IT or intraventricularly weekly for 4 weeks then monthly for 1 year. Patients also receive cranial radiotherapy during consolidation therapy 5 days a week for 2.5 weeks. Patients with A1 bone marrow receive consolidation therapy following completion of induction therapy and blood count recovery. Patients receive consolidation therapy consisting of cyclophosphamide IV on days 1, 15, and 29, cytarabine IV on days 2-5, 9-12, 16-19, and 23-26, oral mercaptopurine on days 1-28, and methotrexate IT on days 2, 9, 16, and 23. Following completion of consolidation therapy, patients eligible for allogeneic bone marrow transplantation receive total body radiotherapy 3 times a day on days -7, -6, -5, and twice on day -4, and eptoposide IV over 4 hours on day -3. Patients undergo allogeneic bone marrow transplantation on day 0. Following completion of consolidation therapy, patients ineligible for allogeneic bone marrow transplantation receive maintenance therapy consisting of oral mercaptopurine on days 1-63, and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients receive subsequent courses of maintenance therapy when blood counts recover. Patients receive a second course of maintenance therapy consisting of vincristine IV on days 1, 8, 15, and 22, doxorubicin IV on days 1, 8, 15, and 22, and oral dexamethasone on days 1-28. Patients receive a third course consisting of cyclophosphamide IV on day 1, oral thioguanine on days 1-14, and cytarabine IV on days 3-6 and 10-13. Patients receive a fourth course consisting of oral mercaptopurine and oral methotrexate daily for 2 years. Patients are followed monthly for 6 months and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study.

Conditions

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Leukemia Neutropenia Thrombocytopenia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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asparaginase

10,000 units/d IV or IM 15 - 24

Intervention Type DRUG

cyclophosphamide

con: 650 mg/m2 IV 1, 15, 29 maint: 650 mg/m2 IV 1

Intervention Type DRUG

cytarabine

cons: 75 mg/m2/d IV Push 2 - 5, 9 - 12, 6 - 19, 23 - 26

Intervention Type DRUG

daunorubicin hydrochloride

ind: 60 mg/m2 IV 22 and 23

Intervention Type DRUG

dexamethasone

main: 10 mg/m2/day PO 1 - 28

Intervention Type DRUG

doxorubicin hydrochloride

main: 25 mg/m2 IV 1, 8, 15, and 22

Intervention Type DRUG

etoposide

60 mg/kg based on ideal body weight day -3

Intervention Type DRUG

leucovorin calcium

5 mg q 6 hours for 4 doses, PO 1, 3, 8, 11 after each methotrexate if WBC \< 3,000 /μl

Intervention Type DRUG

mercaptopurine

con: 60 mg/m2 PO 1 - 28

Intervention Type DRUG

methotrexate

10 mg/m2 IT or IV, d 2, 9, 16, and 23; Maximum 15 mg/admin

Intervention Type DRUG

prednisone

ind: 60 mg/m2/d PO 1 - 21\*, 22 - 28 Patients will receive full dose through day 8 and then tapered to zero between Day 29 and 42.

ind2: 60 mg/m2/d PO through day 42

Intervention Type DRUG

thioguanine

main: 60 mg/m2/day PO 1 - 14

Intervention Type DRUG

vincristine sulfate

ind: 1.4 mg/m2 2 mg max, IV 1, 8, 15, and 22 ind2: 1.4 mg/m2 2 mg max IV 29 and 36 main: 1.5 mg/m2 2 mg max, IV 1, 8, 15, and 22

Intervention Type DRUG

allogeneic bone marrow transplantation

day 0

Intervention Type PROCEDURE

radiation therapy

day -7 through day -4 total dose of radiation is 1,320 cGy.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed acute lymphocytic leukemia FAB class L1-L2 Mixed immunophenotypic markers with no cytochemical myeloid markers allowed No non-Hodgkin's lymphoma No chronic myelogenous leukemia in blast crisis Concurrent registration on the cytogenetics protocol SWOG-9007 required

PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: SWOG 0-3 Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times normal (unless elevation due to leukemia) AST no greater than 3 times normal (unless elevation due to leukemia) No chronic liver disease Renal: Creatinine no greater than 2 times normal Cardiovascular: Left ventricular ejection fraction at least 50% by MUGA or echocardiogram No symptomatic congestive heart failure No symptomatic coronary artery disease No cardiomyopathy No uncontrolled arrhythmia Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior remission induction chemotherapy for acute lymphocytic leukemia
Minimum Eligible Age

15 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen J. Forman, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

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MBCCOP - University of South Alabama

Mobile, Alabama, United States

Site Status

CCOP - Greater Phoenix

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Phoenix (Hayden)

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Tucson

Tucson, Arizona, United States

Site Status

Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Veterans Affairs Medical Center - Little Rock (McClellan)

Little Rock, Arkansas, United States

Site Status

Beckman Research Institute, City of Hope

Duarte, California, United States

Site Status

Veterans Affairs Medical Center - Long Beach

Long Beach, California, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Veterans Affairs Outpatient Clinic - Martinez

Martinez, California, United States

Site Status

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States

Site Status

David Grant Medical Center

Travis Air Force Base, California, United States

Site Status

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States

Site Status

University of Colorado Cancer Center

Denver, Colorado, United States

Site Status

CCOP - Atlanta Regional

Atlanta, Georgia, United States

Site Status

Dwight David Eisenhower Army Medical Center

Fort Gordon, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)

Hines, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

CCOP - Central Illinois

Springfield, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Lexington

Lexington, Kentucky, United States

Site Status

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Veterans Affairs Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

Louisiana State University Hospital - Shreveport

Shreveport, Louisiana, United States

Site Status

Veterans Affairs Medical Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Boston (Jamaica Plain)

Jamaica Plain, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Ann Arbor

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Veterans Affairs Medical Center - Detroit

Detroit, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Site Status

Providence Hospital - Southfield

Southfield, Michigan, United States

Site Status

Veterans Affairs Medical Center - Biloxi

Biloxi, Mississippi, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Jackson

Jackson, Mississippi, United States

Site Status

Keesler Medical Center - Keesler AFB

Keesler Air Force Base, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Site Status

St. Louis University Health Sciences Center

St Louis, Missouri, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Veterans Affairs Medical Center - Albuquerque

Albuquerque, New Mexico, United States

Site Status

University of New Mexico Cancer Research & Treatment Center

Albuquerque, New Mexico, United States

Site Status

Veterans Affairs Medical Center - Brooklyn

Brooklyn, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Barrett Cancer Center, The University Hospital

Cincinnati, Ohio, United States

Site Status

Veterans Affairs Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Kettering, Ohio, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Veterans Affairs Medical Center - Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

Oregon Cancer Center at Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

CCOP - Greenville

Greenville, South Carolina, United States

Site Status

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Texas Tech University Health Science Center

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - Temple

Temple, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Veterans Affairs Medical Center - Salt Lake City

Salt Lake City, Utah, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Veterans Affairs Medical Center - Seattle

Seattle, Washington, United States

Site Status

CCOP - Northwest

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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Pullarkat V, Slovak ML, Kopecky KJ, Forman SJ, Appelbaum FR. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008 Mar 1;111(5):2563-72. doi: 10.1182/blood-2007-10-116186. Epub 2007 Dec 21.

Reference Type RESULT
PMID: 18156492 (View on PubMed)

Sala-Torra O, Gundacker HM, Stirewalt DL, Ladne PA, Pogosova-Agadjanyan EL, Slovak ML, Willman CL, Heimfeld S, Boldt DH, Radich JP. Connective tissue growth factor (CTGF) expression and outcome in adult patients with acute lymphoblastic leukemia. Blood. 2007 Apr 1;109(7):3080-3. doi: 10.1182/blood-2006-06-031096.

Reference Type RESULT
PMID: 17170128 (View on PubMed)

Sala-Torra O, Gundacker HM, Stirewalt DL, et al.: CTGF (CCN2) predicts OS and DFS in adult acute lymphoblastic leukemia. [Abstract] Blood 106 (11): A-336, 2005.

Reference Type RESULT

Slovak ML, Kopecky KJ, Gundacker H, et al.: Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia (ALL): a Southwest Oncology Group (SWOG) study (S9400). [Abstract] Blood 102 (11 Pt 1): A-2223, 2003.

Reference Type RESULT

Boldt DH, Gundacker HM, Lee DY, et al.: Analysis of multidrug resistance gene-1 (MDR1) expression and function in adult acute lymphoblastic leukemia (ALL). A Southwest Oncology Group (SWOG) study. [Abstract] Blood 100 (11 Pt 1): A-2991, 2002.

Reference Type RESULT

Gazitt Y, Lee D, Wang ME, et al.: Functional MDR1 expression in adult acute lymphoblastic leukemia (ALL). Blood 92 (10 Suppl 1): A-2788, 676a, 1998.

Reference Type RESULT

Other Identifiers

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SWOG-9400

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

SWOG-9400

Identifier Type: -

Identifier Source: org_study_id

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