Phase I/II Study of an "Up-Front" Therapeutic Window with 6-MP Followed by Intensified Systemic Induction, Consolidation, and Intensification with Intrathecal Therapy Followed by Delayed Craniospinal Irradiation in Children with Isolated CNS Leukemia
Basic Trial Information
|Phase II, Phase I||Treatment||Completed||over 1 to 21||NCI||POG-9061|
I. Determine the efficacy and toxicity of intensified systemic treatment with delayed craniospinal irradiation in children with acute lymphoblastic leukemia and isolated central nervous system (CNS) disease. II. Describe the pharmacokinetics and cytotoxic effect within the cerebrospinal fluid (CSF) of intravenous 6-mercaptopurine given as a single agent in an up-front window, and determine the level at which 100% of the blasts are cleared from the CSF. III. Measure parameters of CNS tissue injury (free fatty acids and phospholipids in the CSF), and associate these with the effects of CNS leukemia and treatments.
ALL in first bone marrow remission (on or off therapy) with isolated initial CNS relapse Confirmation of CNS relapse in CSF by the presence of more than 5 WBC/mcl with blasts on cytospin/Wright stain exam required (cytomorphology must be confirmed by reference laboratory) If 5 or fewer WBC with blasts or more than 5 WBC with equivocal blasts are detected, LP should be repeated q 2-4 weeks while the patient is off intrathecal chemotherapy until the criterion for CNS disease is met CSF samples may be sent for immunophenotyping
Biologic therapy: Not specified Chemotherapy: Prior anthracycline dose less than 375 mg/sqm Interval of at least 1 week between prior intrathecal or intravenous chemotherapy and initiation of treatment with intravenous 6-mercaptopurine Endocrine therapy: Not specified Radiotherapy: No prior brain irradiation Surgery: Not specified
Age: Children greater than 1 at time of CNS relapse Performance status: Not specified Hematopoietic: ANC greater than 500 Platelets greater than 100,000 Hepatic: Bilirubin less than 2.0 mg/dl SGPT less than 2.5 x normal Renal: Not specified
A maximum of 40 patients will be studied to determine the MTD or optimum dose of 6-MP in the Phase I portion of the study, and a minimum of 30 patients will be entered in the Phase II portion. If 4 or more patients experience CNS failure within 6 months of follow-up, the study may be terminated. An accrual rate of 18 patients/month is anticipated, with an estimated 20-27 months required for completion of accrual.
Nonrandomized study. Patients with significant symptoms (e.g., cranial nerve palsy, seizures, or paresis) or with abnormal liver function are entered directly on the Induction regimen; all other patients begin on the Preinduction regimen. Preinduction: Single-Agent Chemotherapy. 6-Mercaptopurine, 6-MP, NSC-755. Induction: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. Dexamethasone, DM, NSC-34521; Vincristine, VCR, NSC-67574; Daunorubicin, DNR, NSC-82151; plus TIT: Methotrexate, MTX, NSC-740; Hydrocortisone, HC, NSC-10483; Cytarabine, Cytosine arabinoside, ARA-C, NSC-63878. Consolidation: 2-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation plus Triple Intrathecal Therapy. High-dose ARA-C; PEG-L-Asparaginase, PEG-ASP, NSC-624239; with Granulocyte Colony Stimulating Factor (Amgen), G-CSF, NSC-614629; plus TIT. Intensification: 4-Drug Combination Chemotherapy with Leucovorin Rescue and Urothelial Protection plus Triple Intrathecal Therapy. MTX; 6-MP; Etoposide, VP-16, NSC-141540; Cyclophosphamide, CTX, NSC-26271; with Leucovorin calcium, LV, NSC-3590; and Mesna, NSC-113891; plus TIT. Delayed Craniospinal Irradiation: Radiotherapy plus 3-Drug Combination Chemotherapy with (as indicated) Hematologic Toxicity Attenuation. Craniospinal Irradiation using megavoltage equipment (accelerator beams with energies of 4-6 MeV or Co60); plus DM; VCR; PEG-ASP; with (as indicated) G-CSF. Maintenance: 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. 6-MP; MTX; alternating with VCR; CTX.
Ritchey AK, Pollock BH, Lauer SJ, et al.: Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study . J Clin Oncol 17 (12): 3745-52, 1999.[PUBMED Abstract]
Eapen M, Zhang MJ, Devidas M, et al.: Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia 22 (2): 281-6, 2008.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Pediatric Oncology Group
Ph: 304-293-1217; 877-427-2894
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.