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Combination Chemotherapy and Radiation Therapy in Treating Children With Acute Lymphoblastic Leukemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: December 10, 1999
Last updated: January 6, 2010
Last verified: January 2010

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known which treatment regimen is more effective for acute lymphoblastic leukemia.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy and radiation therapy in treating children who have acute lymphoblastic leukemia.

Condition Intervention Phase
Cardiac Toxicity
Drug: asparaginase
Drug: cytarabine
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: methylprednisolone
Drug: prednisolone
Drug: prednisone
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Procedure: quality-of-life assessment
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Treatment of Childhood Acute Lymphoblastic Leukemia: Grant Application Title: Erwinia Asparaginase in Childhood Acute Leukemia

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 420
Study Start Date: January 1996
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Detailed Description:

OBJECTIVES: I. Compare the efficacy and toxicity of doxorubicin with or without the cardioprotectant drug dexrazoxane in children with high risk acute lymphoblastic leukemia. II. Compare the efficacy and toxicity of hyperfractionated cranial radiation plus standard vs intensive intrathecal chemotherapy in preventing CNS leukemia in standard risk patients. III. Compare the efficacy and toxicity of hyperfractionated vs conventionally fractionated cranial radiation plus standard intrathecal chemotherapy in high risk patients. IV. Compare quality of life of these patients. V. Determine whether molecular evidence of leukemia is present in the bone marrow and peripheral blood at the time of remission induction and during intensification and continuation therapy and whether it disappears, changes over time, and is predictive of relapse.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk group (standard risk AND 2 to 8 years AND highest pretreatment WBC less than 20,000/mm3 vs all other standard risk vs high risk). The high risk stratum is further stratified according to dexrazoxane administration (yes vs no). Doxorubicin Investigational Window: Standard risk patients: Patients receive doxorubicin IV on days 0 and 1. High risk patients are randomized to one of two treatment arms: Arm I: Patients receive doxorubicin IV on days 0 and 1. Arm II: Patients receive dexrazoxane IV over 15 minutes immediately followed by doxorubicin IV on days 0 and 1. Induction Therapy for Patients Eligible for Investigational Window: Patients receive oral prednisone or prednisolone or methylprednisolone IV every 6 hours on days 2-30. Patients also receive vincristine IV on days 2, 9, 16, and 23; methotrexate IV over 1 hour on day 2; leucovorin calcium orally or IV every 6 hours beginning 36 hours after methotrexate; and E. coli asparaginase IM on day 4. Intrathecal methotrexate, cytarabine, and hydrocortisone are administered on days 16 and 30. Induction Therapy for Patients Ineligible for Investigational Window: Patients receive the same chemotherapy but at different timing intervals, which are determined by bilirubin levels. Patients who are in hematologic remission on day 30 proceed to CNS treatment. Patients who do not achieve remission by day 30 continue vincristine IV weekly for 3 weeks or until complete remission. Patients who do not achieve remission by day 51 are taken off study. Patients who are in hematologic remission but have CNS blasts on day 30 continue intrathecal chemotherapy, vincristine IV, and asparaginase IM weekly for 3 weeks (days 30, 37, and 44), and doxorubicin IV (with or without dexrazoxane, depending on earlier randomization) on day 30. Cranial radiation is delayed until CSF is clear. CNS Treatment for Standard Risk Patients: Patients receive chemotherapy consisting of vincristine IV for one dose and oral mercaptopurine for 14 days. Patients are then randomized to one of two treatment arms: Arm I: Patients undergo cranial radiotherapy twice a day for 10 days and receive intrathecal methotrexate and cytarabine twice weekly for 2 weeks. Arm II: Patients receive intrathecal methotrexate, cytarabine, and hydrocortisone twice weekly for 2 weeks. Girls with pretreatment WBC less than 20,000/mm3 are nonrandomly assigned to this arm. Patients who refuse randomization undergo conventional radiotherapy daily for 10 days plus receive intrathecal methotrexate and cytarabine twice weekly for 2 weeks. CNS Treatment for High Risk Patients At Least 365 Days Old: Patients receive the same chemotherapy regimen as standard risk patients, plus they receive intrathecal methotrexate and cytarabine twice weekly for 2 weeks. Patients receive doxorubicin with or without dexrazoxane as in the earlier randomization, then are randomized to one of two radiotherapy arms: Arm I: Patients undergo cranial radiotherapy daily for 10 days. Arm II: Patients undergo cranial radiotherapy twice daily for 10 days. Patients who refuse randomization receive therapy as in arm I. Intensification and Continuation Therapy for Patients At Least 365 Days Old: Therapy begins after CNS treatment and at least 3 weeks after complete remission is documented. Standard Risk: Patients receive vincristine IV every 3 weeks, oral prednisone or prednisolone twice a day for five days every 3 weeks, and oral mercaptopurine for 14 days every 3 weeks. E. coli asparaginase IM followed by methotrexate IV or IM are administered weekly for 18 weeks. Treatment is repeated as a 3 week sequence until continuous complete remission has been achieved for 24 months. Patients who had radiotherapy now receive intrathecal methotrexate and cytarabine every 18 weeks, while those patients who did not undergo radiotherapy receive intrathecal methotrexate, cytarabine, and hydrocortisone every 9 weeks for 6 doses, then every 18 weeks. High Risk: Patients receive vincristine, prednisone or prednisolone, mercaptopurine, asparaginase, and methotrexate as for standard risk patients. According to prior randomization, patients also receive doxorubicin IV every 3 weeks or dexrazoxane IV over 15 minutes and doxorubicin IV every 3 weeks. Doxorubicin is continued for 9 months or until the total cumulative dose is reached, then methotrexate IV is administered weekly. Treatment continues as for standard risk patients. Quality of life is assessed on induction day 23, during the second week of CNS therapy or at the start of intensification therapy, during the third week of intensification, during the first week of maintenance therapy (18 months after diagnosis), then every 2 years thereafter. Patients are followed every month for 6 months, every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 420 patients will be accrued for this study within 4 years.


Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

DISEASE CHARACTERISTICS: Histologically or cytologically proven acute lymphoblastic leukemia (ALL) No mature B-cell ALL (i.e., surface immunoglobulin present and L3 morphology) Standard risk disease at diagnosis defined as: 1 to 9 years at diagnosis Highest pretreatment WBC less than 50,000/mm3 No blasts on CSF cytospin No T-cell markers on lymphoblasts No anterior mediastinal mass No cranial nerve palsy High risk disease defined as any patient who fails to meet all standard risk criteria at either diagnosis or at end of induction No t(8;14) (q24;q32), t(8;22), or t(2;8) T-cell surface markers and t(8;14) (q24;q11) allowed Investigational Window eligibility: At least 30 days since prior steroid therapy No concurrent emergent mediastinal radiotherapy or intubation No septic shock No concurrent intracranial hemorrhage No clinical evidence of CNS or lung leukostasis Bilirubin less than 1.4 mg/dL

PATIENT CHARACTERISTICS: Age: 1 to 17 Performance status: Not specified Hematopoietic: See Disease Characteristics Hepatic: See Disease Characteristics Renal: Not specified Other: HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: See Disease Characteristics No more than 1 week of steroids Radiotherapy: See Disease Characteristics Prior emergent radiotherapy to the mediastinum allowed Surgery: Not specified Other: Prior leukapheresis or exchange transfusion allowed, but must be completed before study

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Please refer to this study by its identifier: NCT00004034

United States, Louisiana
Ochsner Clinic
New Orleans, Louisiana, United States, 70121
United States, Maine
Maine Children's Cancer Program
Portland, Maine, United States, 04101
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
University of Rochester Cancer Center
Rochester, New York, United States, 14642
Canada, Ontario
McMaster Division
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Laval University Medical Center
Sainte-Foy, Quebec, Canada, G1V 4G2
Puerto Rico
San Jorge Childrens Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Dana-Farber Cancer Institute
Study Chair: Stephen E. Sallan, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Li A, Zhou J, Wang H, et al.: Molecular analysis of T-cell receptor gene rearrangements in children with T-cell acute lymphoblast leukemia on DFCI ALL Consortium Protocol 95-01. [Abstract] Blood 104 (11): A-1084, 2004.
Silverman LB, Levy DE, Dalton VK, et al.: Outcome of Dana-Farber Cancer Institute (DFCI) Consortium protocol 95-01 for children with newly diagnosed acute lymphoblastic leukemia (ALL). [Abstract] Blood 104 (11): A-679, 2004.
Zhou J, Li A, Goldwasser MA, et al.: Quantitative analysis of minimal residual disease at the completion of induction therapy predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium protocol 95-01. [Abstract] Blood 104 (11): A-323, 2004. Identifier: NCT00004034     History of Changes
Other Study ID Numbers: CDR0000066202, DFCI-95001, DFCI-FDR001197, NCI-G99-1651
Study First Received: December 10, 1999
Last Updated: January 6, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
cardiac toxicity

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Cortisol succinate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Liposomal doxorubicin
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents processed this record on November 27, 2014