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

Leukemia Clinical Trial

Official title:

TREATMENT OF ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: PHASE II TRIALS OF AN INDUCTION REGIMEN INCLUDING PEG-L-ASPARAGINASE, WITH OR WITHOUT PIXY, IN PREVIOUSLY UNTREATED PATIENTS, FOLLOWED BY ALLOGENEIC BONE MARROW TRANSPLANTATION OR FURTHER CHEMOTHERAPY IN FIRST COMPLETE REMISSION

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002665
• Other study ID #: SWOG-9400
• Secondary ID: SWOG-9400U10CA03
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: March 5, 2015
• Start date: July 1995
• Est. completion date: December 2003

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• 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. 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2003
• Est. primary completion date: December 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Neutropenia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• asparaginase
10,000 units/d IV or IM 15 - 24
• cyclophosphamide
con: 650 mg/m2 IV 1, 15, 29 maint: 650 mg/m2 IV 1
• cytarabine
cons: 75 mg/m2/d IV Push 2 - 5, 9 - 12, 6 - 19, 23 - 26
• daunorubicin hydrochloride
ind: 60 mg/m2 IV 22 and 23
• dexamethasone
main: 10 mg/m2/day PO 1 - 28
• doxorubicin hydrochloride
main: 25 mg/m2 IV 1, 8, 15, and 22
• etoposide
60 mg/kg based on ideal body weight day -3
• leucovorin calcium
5 mg q 6 hours for 4 doses, PO 1, 3, 8, 11 after each methotrexate if WBC < 3,000 /µl
• mercaptopurine
con: 60 mg/m2 PO 1 - 28
• methotrexate
10 mg/m2 IT or IV, d 2, 9, 16, and 23; Maximum 15 mg/admin
• 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
• thioguanine
main: 60 mg/m2/day PO 1 - 14
• 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

Procedure:
• allogeneic bone marrow transplantation
day 0

Radiation:
• radiation therapy
day -7 through day -4 total dose of radiation is 1,320 cGy.

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Research & Treatment Center	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi
United States	Boston Medical Center	Boston	Massachusetts
United States	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	Beckman Research Institute, City of Hope	Duarte	California
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts
United States	CCOP - Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	CCOP - Dayton	Kettering	Ohio
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	MBCCOP - University of South Alabama	Mobile	Alabama
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Hospital - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Central Illinois	Springfield	Illinois
United States	CCOP - Northwest	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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.

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.

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. Epub 2007 Dec 21. — View Citation

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.

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. 2 — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response			No