Trial Information

TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY

OBJECTIVES:

I. Determine the efficacy and toxicity of intensified systemic treatment with delayed
central nervous system (CNS) irradiation in children with acute lymphoblastic leukemia and
isolated CNS disease.

II. Determine the efficacy of systemic thiotepa in reducing or clearing blasts in the
cerebrospinal fluid of these patients.

III. Evaluate the toxicity of single dose thiotepa followed by dexamethasone, vincristine,
daunorubicin, and triple intrathecal therapy in these patients.

IV. Determine the response rate of intrathecal sustained release cytarabine (DTC101) in
patients with first bone marrow remission with first isolated CNS relapse.

V. Assess the safety and toxicity of DTC101 in these patients.

OUTLINE:

Patients with significant neurologic symptoms (e.g., seizures, cranial nerve palsy, paresis,
mental status changes) are entered directly on the Induction regimen and do not receive the
Therapeutic Window. The following acronyms are used: ARA-C Cytarabine, NSC-63878 ASP
Asparaginase, NSC-109229 (E. coli) or 106977 (Erwinia) CF Leucovorin calcium, NSC-3590 CTX
Cyclophosphamide, NSC-26271 DM Dexamethasone, NSC-34521 DNR Daunorubicin, NSC-82151 DTC101
Sustained release cytarabine G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629
HC Hydrocortisone, NSC-10483 Mesna Mercaptoethane sulfonate, NSC-113891 MP Mercaptopurine,
NSC-755 MTX Methotrexate, NSC-740 TIT Triple Intrathecal Therapy, IT MTX/IT HC/IT ARA-C
TMP-SMX Trimethoprim-sulfamethoxazole TSPA Thiotepa, NSC-6396 VCR Vincristine, NSC-67574
VP-16 Etoposide, NSC-141540

THERAPEUTIC WINDOW: Single Agent Chemotherapy. TSPA or DTC101. ** Thiotepa window closed as
of 7/6/98 ** ** DTC101 window opened 11/15/99 **

INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus
TIT.

CONSOLIDATION: 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP;
plus TIT.

INTENSIFICATION I: 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple
Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT.

RE-INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR;
plus TIT.

INTENSIFICATION II: 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple
Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT.

CHEMORADIOTHERAPY: Radiotherapy plus 3-Drug Combination Chemotherapy. Craniospinal
irradiation using x-rays with energies of 4-6 MV (electrons acceptable for spinal cord
irradiation); plus ASP/DM/VCR.

MAINTENANCE: 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination
Chemotherapy. MP/MTX; alternating with CTX/VCR.