Clinical trial NCT00981799
Conditions: Relapsed T-Cell Acute Lymphoblastic Leukemia Relapsed T-Cell Lymphoblastic Lymphoma
Keywords: Relapse T cell Lymphoblastic Leukemia Lymphoma Nelarabine TACL NECTAR
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2010-06-01; Completion date: 2016-07-18
Enrollment: 23 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Nelarabine has shown significant activity in patients with T-cell malignancies. This study will determine the safety and maximum tolerated dose of the combination of nelarabine, cyclophosphamide and etoposide in patients with first bone marrow relapse of T-ALL, or first relapse of T-LL.

Detailed description:

Arms: arm 1: The study will begin at Dose Level 1 at 480 mg/m2 Nelarabine (75% of single agent maximum tolerated dose) and 330 mg/m2 Cyclophospamide and will escalate to the next Dose Level if the maximum tolerated dose (MTD) is not exceeded. The first 3 patients will be enrolled into Dose Level 1. If 0/3 experiences dose limiting toxicity (DLT) at a given dose level, then the dose is escalated to the next higher level and 3 more patients are enrolled. If 1/3 experiences DLT at current dose, the up to 3 more patients are accrued at the same dose level. If 2 or more DLTs are observed in a 3-patient or 6-patient cohort at a given dose level, then the MTD has been exceeded, dose escalation will be stopped, and up to 3 additional patients will be enrolled at the next lower dose level (unless 6 patients have already been treated at that prior dose). If the MTD is exceeded at Dose Level 0, the study will be closed. arm 2: Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 330 mg/m2 Cyclophosphamide. arm 3: Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 400 mg/m2 Cyclophosphamide arm 4: Patients in this arm will be administered Nelarabine 325 mg/m2 (50% of single agent MTD) and 330 mg/2 Cyclophosphamide. Patients will only enter this arm if the MTD at Dose Level 1 has been exceeded. If the MTD is exceeded at Dose Level 0, the study will be closed.
Interventions: intervention 1: Nelarabine intervention 2: Etoposide intervention 3: Cyclophosphamide intervention 4: Methotrexate intervention 5: Filgrastim
Intervention descriptions: intervention 1: Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5. intervention 2: 100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5 intervention 3: Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5. intervention 4: Give between day 29 and 36 or when ANC\>750 and PLTS\>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.

Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but \<2 years of age 10 mg for patients age greater than or equal to 2, but \<3 years of age 12 mg for patients greater than or equal to 3, but \< 9 years of age 15 mg for patients greater than or equal to \>9 years of age intervention 5: 5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000/mm3 for two consecutive days.

Protocol documents: