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

NCT00002961 | Terminated Phase 3

• 4 other identifiers: 1995-9-1013CHP-BMT-583BMS-CHP-BMT-583NCI-V97-1183
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 18

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.

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission

Study Arms (2)

Total body irradiation

ACTIVE COMPARATOR

Total body irradiation 1200 centigray

Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Radiation: Total Body Irradiation; Radiation: Radiation

Busulfan

ACTIVE COMPARATOR

Busulfan 16 doses

Drug: cyclophosphamide; Drug: cyclosporine; Drug: etoposide; Drug: methotrexate; Procedure: allogeneic bone marrow transplantation; Drug: Busulfan; Drug: Mesna; Radiation: Radiation

Interventions

cyclophosphamide DRUG

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

Also known as: Cytoxin

Busulfan; Total body irradiation

cyclosporine DRUG

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.

Busulfan

etoposide DRUG

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

Also known as: Etopophos, etoposide phosphate, VP-16

Busulfan; Total body irradiation

methotrexate DRUG

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.

Also known as: MTX

Busulfan

allogeneic bone marrow transplantation PROCEDURE

Bone marrow infusion given on day 0

Also known as: BMT

Busulfan; Total body irradiation

Total Body Irradiation RADIATION

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) \[200 cGy twice a day (BID)\].

Also known as: TBI

Total body irradiation

Busulfan DRUG

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.

Also known as: Myleran

Busulfan

Mesna DRUG

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.

Also known as: Mesnex

Busulfan

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-

Busulfan; Total body irradiation

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (18)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Children's Hospital and Health Center

San Diego, California, 92123-4282, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637, United States

Location

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, 40536-0084, United States

Location

Louisiana State University School of Medicine

New Orleans, Louisiana, 70112-2822, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

Ireland Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Palmetto Richland Memorial Hospital

Columbia, South Carolina, 29203, United States

Location

South Texas Cancer Institute

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84132, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T2T 5C7, Canada

Location

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Cyclosporine; Etoposide; etoposide phosphate; Methotrexate; Whole-Body Irradiation; Busulfan; Mesna; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Sulfhydryl Compounds; Physical Phenomena

Study Officials

• Nancy Bunin, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: May 19, 2004
• Study Start: October 1, 1995
• Primary Completion: February 1, 2001
• Study Completion: February 1, 2001
• Last Updated: October 16, 2013

Record last verified: 2013-10

Locations

CA (1); US (17)