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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00002665
First received: November 1, 1999
Last updated: January 12, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Neutropenia
Thrombocytopenia
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Procedure: allogeneic bone marrow transplantation
Radiation: radiation therapy
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • response [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: July 1995
Study Completion Date: December 2003
Primary Completion Date: December 2001 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: asparaginase
    10,000 units/d IV or IM 15 - 24
    Drug: cyclophosphamide
    con: 650 mg/m2 IV 1, 15, 29 maint: 650 mg/m2 IV 1
    Drug: cytarabine
    cons: 75 mg/m2/d IV Push 2 - 5, 9 - 12, 6 - 19, 23 - 26
    Drug: daunorubicin hydrochloride
    ind: 60 mg/m2 IV 22 and 23
    Drug: dexamethasone
    main: 10 mg/m2/day PO 1 - 28
    Drug: doxorubicin hydrochloride
    main: 25 mg/m2 IV 1, 8, 15, and 22
    Drug: etoposide
    60 mg/kg based on ideal body weight day -3
    Drug: leucovorin calcium
    5 mg q 6 hours for 4 doses, PO 1, 3, 8, 11 after each methotrexate if WBC < 3,000 /μl
    Drug: mercaptopurine
    con: 60 mg/m2 PO 1 - 28
    Drug: methotrexate
    10 mg/m2 IT or IV, d 2, 9, 16, and 23; Maximum 15 mg/admin
    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

    Drug: thioguanine
    main: 60 mg/m2/day PO 1 - 14
    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
    Procedure: allogeneic bone marrow transplantation
    day 0
    Radiation: radiation therapy
    day -7 through day -4 total dose of radiation is 1,320 cGy.
Detailed 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.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002665

  Show 83 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Stephen J. Forman, MD Beckman Research Institute
  More Information

Additional Information:
Publications:
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.
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.
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.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00002665     History of Changes
Other Study ID Numbers: CDR0000064250, SWOG-9400, U10CA032102
Study First Received: November 1, 1999
Last Updated: January 12, 2012
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
untreated adult acute lymphoblastic leukemia
L1 adult acute lymphoblastic leukemia
L2 adult acute lymphoblastic leukemia
L3 adult acute lymphoblastic leukemia
neutropenia
thrombocytopenia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neutropenia
Thrombocytopenia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Blood Platelet Disorders
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Etoposide
Prednisone
Vincristine
BB 1101
Dexamethasone acetate

ClinicalTrials.gov processed this record on July 20, 2014