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

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002785

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

128

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: cyclosporine Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: mesna Drug: methotrexate Drug: methylprednisolone Drug: pegaspargase Drug: prednisone Drug: therapeutic hydrocortisone Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET photon therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Infants Less Than 1 Year of Age.

Study Start Date :

Jul 1, 1996

Actual Primary Completion Date :

Aug 1, 2000

Actual Study Completion Date :

Mar 1, 2007

Outcome Measures

Primary Outcome Measures

Event Free Survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
3	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
4	Children's Hospital of Orange County	Orange	California	United States	92668
5	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
6	Children's Hospital of Denver	Denver	Colorado	United States	80218
7	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
8	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
9	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5265
10	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
11	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
12	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
13	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
14	Children's Mercy Hospital - Kansas City	Kansas City	Missouri	United States	64108
15	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
16	Kaplan Cancer Center	New York	New York	United States	10016
17	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
18	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
19	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
20	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio	United States	45229-3039
21	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
22	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
23	Doernbecher Children's Hospital	Portland	Oregon	United States	97201-3098
24	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
25	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
26	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
27	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
28	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
29	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
30	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
31	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
32	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
33	IWK Grace Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9