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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase II, Phase ITreatment1 to 21T2008-002
NCI-2011-02779, NCT00981799

Trial Description

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.

Eligibility Criteria

Inclusion Criteria:

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

study.

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

hemipelvic radiation.

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

phase.

Exclusion Criteria:

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

infection.

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

neurologist.

Patients with Down syndrome are excluded.

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Therapeutic Advances in Childhood Leukemia Consortium

  • GlaxoSmithKline

Trial Sites

U.S.A.

California
Los Angeles

Children's Hospital Los Angeles

Paul S. Gaynon
Principal Investigator

Colorado
Aurora

Children's Hospital Colorado

Lia Gore
Principal Investigator

Georgia
Atlanta

Children's Healthcare of Atlanta - Egleston

Todd Michael Cooper
Principal Investigator

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

Patrick A. Brown
Principal Investigator

Massachusetts
Boston

Dana-Farber Cancer Institute

Lewis Barry Silverman
Ph: 866-790-4500
Email: lewis_silverman@dfci.harvard.edu

Lewis Barry Silverman
Principal Investigator

Michigan
Ann Arbor

University of Michigan Comprehensive Cancer Center

Raymond J. Hutchinson
Principal Investigator

New York
New York

Laura and Issac Perlmutter Cancer Center at NYU Langone

Teena Bhatla
Principal Investigator

Ohio
Cleveland

Case Comprehensive Cancer Center

Robin Elizabeth Norris
Principal Investigator

Tennessee
Memphis

St. Jude Children's Research Hospital

Deepa Bhojwani
Principal Investigator

Nashville

Vanderbilt University/Ingram Cancer Center

Haydar A. Frangoul
Principal Investigator

Utah
Salt Lake City

Huntsman Cancer Institute/University of Utah

Anupam Verma
Principal Investigator

Primary Children's Hospital

Elizabeth Ann Raetz
Email: prmc.coordinator@nyumc.org

Elizabeth Ann Raetz
Principal Investigator

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.