Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia

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. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy, radiation therapy, and bone marrow transplantation may kill more cancer cells.

PURPOSE: Randomized phase III trial to compare high-dose chemotherapy with or without total-body irradiation before bone marrow transplantation in treating children with acute lymphoblastic leukemia.

Conditions

• Leukemia

Interventions

DRUG

cyclophosphamide

Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.

DRUG

cyclosporine

graft vs. host disease (GVHD)prophylaxis: starting on day-1, cyclosporin 1.5 mg/kg IV every 12 hours or by continuous infusion. When the patient tolerates adequate oral intake, cyclosporin therapy may be changed from IV to oral administration. Cyclosporin therapy should be continued at full dose until day +50. if the patient has less than Grade 2 GVHD, cyclosporin may be tapered by 5-10% weekly until completely off cyclosporin therapy.

DRUG

etoposide

Day 4 (arms A/B): 40 mg/kg over four hours intravenously

DRUG

methotrexate

methotrexate 15 mg/m2 IV on day +1 (do not give until 24 hours after marrow infusion), and 10mg/mg2 IV on days +3 and +6. Methotrexate may be held after two doses for bilirubin .2 mg/dL. If serum creatinine is \>2x baseline, methotrexate will be omitted. If the presence of ascites or pleural effusion, methotrexate will be omitted.

PROCEDURE

allogeneic bone marrow transplantation

Bone marrow infusion given on day 0

RADIATION

Total Body Irradiation

Day 0: Marrow Transfusion; Day 1: rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6 and 7: Total Body Irradiation (TBI) \[200 cGy twice a day (BID)\].

DRUG

Busulfan

Conditioning Regimen Arm B: Day 0: Marrow infusion; Day 1: Rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6,7 and 8: Busulfan 0.8 mg/kg intravenous (IV) every 6 hours x 4 doses. Patients \</= 20kg to receive busulfan 1.0 mg/kg/dose IV\*\*Busulfan oral preparation may be substituted: 1mg/kg/dose by mouth (po) for patients \>20kg and 1.25 mg/kg/dose by mouth (po) for patients \</= 20 kg.

DRUG

Mesna

Dosing per institutional preference for hemorrhagic cystitis. Mesna 300 mg/m2 as a 15 minute infusion prior to each dose of cyclophosphamide, then at 3,6,9,12, 18 and 21 hours after initiation of each cyclophosphamide infusion. Alternative method of Mesna administration is 10 mg/kg prior to cyclophosphamide and 100 mg/kg/24 hours by continuous infusion.

RADIATION

Radiation

Central Nervous System (CNS) therapy: a) CNS Leukemia prior to study entry: No TBI i) No prior CNS irradiation: 2340 centigray (cGy) in 13 fractions of 180 cGy to the cranial field and 600 cGy in 200 cGy fractions to the spinal field prior to conditioning. II) \>/= 1800 cGy prior CNS irradiation: 1800 cGy to cranial field and 600 cGy spinal prior to conditioning. If prior radiation therapy (RT) doses \>3000 cGy have been administered or CNS Leukemia prior to study entry: TBI, consult with Principal Investigator (PI). Recommend: 1) no prior CNS irradiation: 600 cGy in 3 fractions to the cranial field prior to conditioning or overlapping with TBI. Testicular Boost Irradiation: a) overt testicular leukemia at relapse: No TBI 2400 cGy in 12 fractions prior to conditioning; b) overt testicular leukemia at relapse: TBI 1200 cGy in 6 fractions over 8-10 days prior to conditioning. c) No overt testicular leukemia: 200 cGy first and last fractions of TBI-

Sponsors & Collaborators

• Children's Hospital of Philadelphia

  lead OTHER

Principal Investigators

• Nancy Bunin, MD · Children's Hospital of Philadelphia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1995-10-31

Primary Completion

2001-02-28

Completion

2001-02-28

Countries

• United States
• Canada

Study Locations