NCT00002665

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: SWOG Cancer Research Network · Network
• Sex: All
• Age: 15 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Leukemia
• Neutropenia
• Thrombocytopenia

Interventions

Type	Name	Description
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.

Timeline

• Start date: 1995-07-01
• Primary completion: 2001-12-01
• Completion: 2003-12-01
• First posted: 2004-07-29
• Last updated: 2015-03-06

Locations

83 sites across 1 country: United States