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

Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Pediatric Leukemia
NCT ID: NCT00981799 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 10-052

 

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.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:
Lewis Silverman, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:
Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria: - Patients must have first relapse T-cell ALL or T-cell lymphoblastic lymphoma. - 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.
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