Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL

Inclusion Criteria:

   - Patients to be enrolled in the dose-escalation portion of this study must have T-cell
   ALL or T-cell lymphoblastic lymphoma (LL) in first relapse or must have failed primary
   induction chemotherapy (ie, never attained a complete remission following an initial
   course of standard therapy for T-ALL or T-LL). Patients to be enrolled in the cohort
   expansion portion of this study (ie, those treated at the recommended phase 2 dose)
   must have T-cell ALL in first relapse or must have failed primary induction
   chemotherapy (ie, never attained a complete remission following an initial course of
   standard therapy for T-ALL). T-LL patients are not eligible for the cohort expansion
   phase.

   - Patients with T-cell ALL must have greater than 25% blasts in the bone marrow with or
   without extramedullary disease.

   - Patients with T-cell LL must have recurrent disease, documented by clinical or
   radiographic criteria, as well as histologic verification of the malignancy at
   original diagnosis. Patients with T-cell LL enrolled in the phase I dose-escalation
   study are not required to have measurable disease; however, patients enrolled in the
   phase II cohort expansion at the MTD must have measurable disease.

   - Patients may have CNS 1 or CNS 2 disease but not CNS 3.

   - ECOG 0-2 or Karnofsky ≥ 50% for patients > 16 years of age; Lansky ≥ 50% for patients
   ≤16 years of age.

   - Patients may be enrolled on study regardless of the timing of prior Intrathecal
   therapy; however, they MAY NOT BEGIN TREATMENT ON THIS PROTOCOL UNTIL A MINIMUM OF 7
   DAYS HAS ELAPSED SINCE PRIOR INTRATHECAL THERAPY.

   - At least 6 weeks must have elapsed since administration of nitrosureas.

   - At least 12 weeks must have elapsed since administration of craniospinal or hemipelvic
   radiation.

   - Female patients of childbearing potential must have a negative urine or serum
   pregnancy test confirmed within 2 weeks prior to enrollment.

   - Female patients with infants must agree not to breastfeed their infants while on this
   study.

   - Male and female patients of child-bearing potential must agree to use an effective
   method of contraception approved by the investigator during the study and for a
   minimum of 6 months after study treatment.

   - Adequate renal function defined as serum creatinine ≤ 1.5x upper limit of normal (ULN)
   for age. If the serum creatinine is above these values, the calculated creatinine
   clearance or radioisotope GFR must be ≥ 70 mL/min/1.73m2.

   - Total bilirubin ≤ 1.5x ULN for age. If the total bilirubin is elevated, patient will
   still be eligible if the conjugated (direct) serum bilirubin ≤ ULN for age.

   - ALT ≤ 5x ULN of normal for age.

   - Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram or
   ejection fraction ≥ 45% by gated radionuclide study.

   - No evidence of dyspnea at rest

   - No exercise intolerance

   - A pulse oximetry ≥ 94% at sea level (≥ 90% at altitude ≥ 5000 feet) if there is
   clinical indication for determination.

   - Patients and/or their parents or legal guardians must be capable of understanding the
   investigational nature, potential risks and benefits of the study. All patients and/or
   their parents or legal guardians must sign a written informed consent.

Exclusion Criteria:

   - Patients with Down syndrome are excluded.

   - Patients with pre-existing Grade 2 (or greater) peripheral motor or sensory
   neurotoxicity per the CTCAE 3.0 as determined by the treating physician or a
   neurologist.

   - Patients with a history of prior veno-occlusive disease (VOD) or findings consistent
   with a diagnosis of VOD, defined as: conjugated serum bilirubin >1.4 mg/dL AND
   unexplained weight gain greater than 10% of baseline weight or ascites AND
   hepatomegaly or right upper quadrant pain without another explanation, OR reversal of
   portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.

   - Previous hematopoetic stem cell transplantation.

   - Patients with a prior seizure disorder requiring anti-convulsant therapy are not
   eligible to receive nelarabine. For the purposes of this study, this includes any
   patient that has received anticonvulsant therapy to prevent/treat seizures in the
   prior two years.

   - Positive blood culture within 48 hours of study enrollment.

   - Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection.

   - Plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy
   during the study period.

   - Any significant concurrent disease, illness, psychiatric disorder or social issue that
   would compromise patient safety or compliance, interfere with consent, study
   participation, follow up, or interpretation of study results.