Combination Chemotherapy, Bone Marrow Transplantation, and Radiation Therapy in Treating Infants With Acute Lymphoblastic Leukemia

NCT ID: NCT00002785

Last Updated: 2014-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-07-31
• Study Completion Date: 2007-03-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Bone marrow transplantation may allow the doctor to give higher doses of chemotherapy and kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, bone marrow transplantation, and radiation therapy in treating infants with acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES: I. Assess the feasibility and outcome of intensified induction/consolidation followed by intensified re-induction/re-intensification in infants less than 1 year of age with newly diagnosed acute lymphocytic leukemia (ALL). II. Evaluate the feasibility and outcome of bone marrow transplantation using family or unrelated donors in infants with the 11q23 abnormality. III. Evaluate neuropsychologic outcome upon completion of protocol therapy in patients who have reached the ages of 3 and 7 years, with special attention to the outcome in infants who received total-body irradiation. IV. Study the biology of infant ALL in samples of leukemic blood and bone marrow. V. Study the possible associations among patient- and disease-specific factors and family sociodemographic characteristics that mediate treatment outcome.

OUTLINE: Upon completion of Induction/Intensification and Re-Induction therapy, patients with the 11q23 abnormality and with a matched or one-antigen mismatched related or unrelated donor proceed immediately to Transplantation; all others proceed to Re-Intensification, Consolidation, Intensified Maintenance, and Routine Maintenance. The following acronyms are used: AlBM Allogeneic Bone Marrow ARA-C Cytarabine, NSC-63878 ASP Asparaginase, NSC-109229 CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 CYSP Cyclosporine, NSC-290193 DM Dexamethasone, NSC-34521 DNR Daunorubicin, NSC-82151 G-CSF Granulocyte-Colony Stimulating Factor (Amgen), NSC-614629 HC Hydrocortisone, NSC-10483 MePRDL Methylprednisolone, NSC-19987 Mesna Mercaptoethane sulfonate, NSC-113891 MP Mercaptopurine, NSC-755 MTX Methotrexate, NSC-740 PEG-ASP Pegaspargase, NSC-644954 PRED Prednisone, NSC-10023 TBI Total-Body Irradiation TIT Triple Intrathecal Therapy (IT ARA-C/IT HC/IT MTX) VCR Vincristine, NSC-67574 VH Very High Dose VP-16 Etoposide, NSC-141540 INDUCTION/INTENSIFICATION: 5-Drug Combination Systemic Chemotherapy followed by 3-Drug Combination Systemic Chemotherapy plus 3-Drug Combination Intrathecal Chemotherapy. DM/VCR/DNR/CTX/Mesna/ASP; followed by MTX/CF/VP-16/CTX/Mesna; plus TIT. RE-INDUCTION: 5-Drug Combination Systemic Chemotherapy plus 3-Drug Combination Intrathecal Chemotherapy. DNR/VCR/CTX/Mesna/ASP/DM; plus TIT. RE-INTENSIFICATION: 2-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy followed by 2-Drug Combination Systemic Chemotherapy. VCR/VH MTX/CF; plus IT ARA-C; followed by VP-16/CTX/Mesna. CONSOLIDATION: 2-Drug Combination Systemic Chemotherapy followed by 2-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. ARA-C/ASP; followed by VH MTX/CF/VCR; plus IT ARA-C. INTENSIFIED MAINTENANCE: 4-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy followed by 2-Drug Combination Systemic Chemotherapy. DM/VCR/MTX/MP; plus IT ARA-C followed by VP-16/CTX/Mesna. ROUTINE MAINTENANCE: 4-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. VCR/MTX/MP/PRED; plus IT MTX. TRANSPLANTATION: 2-Drug Combination Myeloablative Chemotherapy followed by Radiotherapy followed by Hematopoietic Rescue plus GVHD Prophylaxis. ARA-C/CTX; followed by TBI using a linear accelerator or Co60 equipment; followed by AlBM; plus MePRDL; CYSP.

PROJECTED ACCRUAL: 100 patients per year will be entered over approximately 3 years.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

asparaginase

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

mercaptopurine

Intervention Type: DRUG

mesna

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

pegaspargase

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

therapeutic hydrocortisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type: RADIATION

low-LET photon therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed acute lymphoblastic leukemia (ALL) in infants under 12 months of age at diagnosis Adequate bone marrow and/or peripheral blood specimens with blasts available No prior treatment for ALL except emergency therapy for the following: Blast cell crisis Superior vena cava syndrome Renal failure due to leukemic infiltration of the kidneys

PATIENT CHARACTERISTICS: See General Eligibility Criteria

• Maximum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patricia A. Dinndorf, MD

Role: STUDY_CHAIR

Children's National Research Institute

Locations

Long Beach Memorial Medical Center

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Children's Hospital of Denver

Denver, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Kaplan Cancer Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Children's Hospital of Columbus

Columbus, Ohio, United States

Doernbecher Children's Hospital

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Vanderbilt Cancer Center

Nashville, Tennessee, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

IWK Grace Health Centre

Halifax, Nova Scotia, Canada

Countries

United States; Australia; Canada

References

Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, Hilden JM, Heerema NA, Sanders JE, McGlennen R, Willman CL, Carroll AJ, Behm F, Smith FO, Woods WG, Godder K, Reaman GH. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group. J Clin Oncol. 2011 Jan 10;29(2):214-22. doi: 10.1200/JCO.2009.26.8938. Epub 2010 Dec 6.

Reference Type: BACKGROUND

PMID: 21135279 (View on PubMed)

Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008 Dec;22(12):2142-50. doi: 10.1038/leu.2008.251. Epub 2008 Sep 25.

Reference Type: BACKGROUND

PMID: 18818707 (View on PubMed)

Salzer W, Dinndorf P, Dreyer Z, Hilden J, Reaman GH. Analysis of infectious complications in infants with acute lymphoblastic leukemia treated on the Children's Cancer Group Protocol 1953: a report from the Children's Oncology Group. J Pediatr Hematol Oncol. 2009 Jun;31(6):398-405. doi: 10.1097/MPH.0b013e3181a6dec0.

Reference Type: RESULT

PMID: 19648788 (View on PubMed)

Robinson BW, Cao K, Hilden JM, et al.: Age is the strongest determinant of leukemia blast cell gene expression in MLL-rearranged infant ALL and MLL-AF4 directs a distinct gene expression profile related to CNS disease. [Abstract] Blood 112 (11): A-1200, 2008.

Reference Type: RESULT

Hilden JM, Dinndorf PA, Meerbaum SO, Sather H, Villaluna D, Heerema NA, McGlennen R, Smith FO, Woods WG, Salzer WL, Johnstone HS, Dreyer Z, Reaman GH; Children's Oncology Group. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group. Blood. 2006 Jul 15;108(2):441-51. doi: 10.1182/blood-2005-07-3011. Epub 2006 Mar 23.

Reference Type: RESULT

PMID: 16556894 (View on PubMed)

Other Identifiers

CCG-1953

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064841

Identifier Type: OTHER

Identifier Source: secondary_id

1953

Identifier Type: -

Identifier Source: org_study_id