Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
Basic Trial Information
|Phase II, Phase I||Treatment||1 to 21||T2008-002|
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.
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.
A pulse oximetry ≥ 94% at sea level (≥ 90% at altitude ≥ 5000 feet) if there is
clinical indication for determination.
No exercise intolerance
No evidence of dyspnea at rest
Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram
or ejection fraction ≥ 45% by gated radionuclide study.
ALT ≤ 5x ULN of normal for age.
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.
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.
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.
Female patients with infants must agree not to breastfeed their infants while on this
Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed within 2 weeks prior to enrollment.
At least 12 weeks must have elapsed since administration of craniospinal or
At least 6 weeks must have elapsed since administration of nitrosureas.
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.
ECOG 0-2 or Karnofsky ≥ 50% for patients > 16 years of age; Lansky ≥ 50% for patients
≤16 years of age.
Patients may have CNS 1 or CNS 2 disease but not CNS 3.
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 with T-cell ALL must have greater than 25% blasts in the bone marrow with or
without extramedullary disease.
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
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.
Plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy
during the study period.
Fever above 38.2 within 48 hours of study enrollment with clinical signs of
Positive blood culture within 48 hours of study enrollment.
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.
Previous hematopoetic stem cell transplantation.
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.
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 Down syndrome are excluded.
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
Children's Hospital Los Angeles
Paul S. Gaynon
Children's Hospital Colorado
Children's Healthcare of Atlanta - Egleston
Todd Michael Cooper
Johns Hopkins University/Sidney Kimmel Cancer Center
Patrick A. Brown
Dana-Farber Cancer Institute
Lewis Barry Silverman
Lewis Barry Silverman
University of Michigan Comprehensive Cancer Center
Raymond J. Hutchinson
Laura and Issac Perlmutter Cancer Center at NYU Langone
Case Comprehensive Cancer Center
Robin Elizabeth Norris
St. Jude Children's Research Hospital
Vanderbilt University/Ingram Cancer Center
Haydar A. Frangoul
Salt Lake City
Huntsman Cancer Institute/University of Utah
Primary Children's Hospital
Elizabeth Ann Raetz
Elizabeth Ann Raetz
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00981799
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.