Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
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.
Dana-Farber Cancer Institute, Children's Hospital Boston
Lewis Silverman, MD,
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute:
Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,
- 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
- 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
- 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.
- 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
- 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
- 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.