Clinical trial NCT00002961: Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia
Official title: Randomized Trial of Busulfan or Total Body Irradiation Conditioning Regimens for Children With Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Leukemia
Keywords: recurrent childhood acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2004-05-19
Enrollment: 43
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

Detailed description: OBJECTIVES: I. Compare the efficacy of a busulfan containing conditioning regimen versus a total body irradiation (TBI) containing regimen for children with acute lymphoblastic leukemia (ALL) undergoing allogeneic bone marrow transplantation. II. Compare relapse rate between a chemotherapy only regimen versus a total body irradiation containing regimen for children with ALL. III. Assess and compare the acute and chronic neuropsychological effects of bone marrow transplantation (BMT) in children undergoing BMT with busulfan or TBI conditioning regimens. IV. Assess and compare the cardiac, pulmonary and growth effects of BMT in children undergoing this conditioning regimen. V. Assess the relationship between plasma busulfan levels and relapse and toxicity. VI. Assess and compare minimal residual disease patterns by quantitative polymerase chain reaction (PCR) in patients receiving busulfan or TBI conditioning regimens.

OUTLINE: This is a multicenter, randomized study comparing a chemotherapy only arm, including busulfan, with a TBI containing arm. Arm I patients receive TBI on days -7, -6, and -5 given in 2 fractions daily. Arm II patients receive busulfan every 6 hours on days -8, -7, -6, and -5. Both regimens are followed by etoposide over 4 hours on day -4 and cyclophosphamide intravenously (IV) on days -3 and -2. Marrow infusion begins following a day of rest. Starting on day -1, cyclosporine IV is administered every 12 hours or by continuous infusion and continues until day 50. Methotrexate IV is administered on days 1, 3, and 6

PROJECTED ACCRUAL: A total of 230 patients will be entered into this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed childhood acute lymphoblastic leukemia (ALL) in second hematologic remission or greater who have relapsed: On therapy OR Within one year of discontinuation of therapy OR Greater than 1 year from discontinuation of high risk intensive therapy (matched sibling donor only) Patients with central nervous system or testicular relapse: Occurred within 18 months of diagnosis OR Following prophylactic or therapeutic cranial irradiation T cell disease with isolated central nervous system (CNS) or bone marrow relapse at any time Patients in first remission with greater than 4 weeks to achieve remission or with high risk features such as: t(4,11) t(9,22) Hypodiploidy Patients under 12 months of age in first remission with any of the following features at diagnosis: CALLA (CD10) negative white blood count (WBC) at least 100,000/mm3 Day 14 M2 or M3 bone marrow CNS disease

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: No active hepatitis B or C Bilirubin no greater than 1.5 times normal Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance at least 65 mL/min Cardiovascular: Shortening fraction greater than 27% by echocardiogram OR Ejection fraction greater than 47% by radionuclide angiogram Pulmonary: \[1\] forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) greater than 60% For uncooperative children: No evidence of dyspnea at rest No exercise intolerance Pulse oximetry greater than 94% Other: No active infection No occult untreated infection HIV negative Not eligible for Children's Cancer Group (CCG) or Pediatric Oncology Group (POG) transplant study Donor criteria: Genotypically matched sibling or phenotypically matched family member (bone marrow or peripheral blood stem cells may be used) One antigen mismatched related donor Matched or one antigen mismatched unrelated donor Cord blood (genotypic or phenotypic match or one antigen mismatch) Matched sibling or phenotypically matched family member peripheral stem cells

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: San Diego
country: United States
facility: Children's Hospital and Health Center
state: California
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Richland Memorial Hospital
state: South Carolina
city: San Antonio
country: United States
facility: South Texas Cancer Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Nancy Bunin, MD
role: STUDY_CHAIR
References: