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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase ITreatmentActive1 to 21OtherT2008-002
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 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Therapeutic Advances in Childhood Leukemia Consortium

  • GlaxoSmithkline
Jim Whitlock, MD, Study Chair
Jeannette van der Giessen, BA
Ph: 323-361-8725
Email: jvandergiessen@chla.usc.edu

Trial Sites

U.S.A.

California
Los Angeles

Children's Hospital Los Angeles

Paul S. Gaynon
Principal Investigator

San Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

Steven DuBois
Principal Investigator

Colorado
Aurora

Children's Hospital Colorado Center for Cancer and Blood Disorders

Lia Gore
Principal Investigator

Florida
Miami

University of Miami Sylvester Comprehensive Cancer Center - Miami

John Goldberg, MD
Principal Investigator

Illinois
Chicago

Ann and Robert H. Lurie Children's Hospital of Chicago

Nobuko Hijiya, MD
Principal Investigator

Michigan
Ann Arbor

C.S. Mott Children's Hospital at University of Michigan Medical Center

Raymond J. Hutchinson
Principal Investigator

Minnesota
Minneapolis

Children's Hospitals and Clinics of Minnesota - Minneapolis

Bruce C. Bostrom
Principal Investigator

Yoav Messinger
Principal Investigator

Missouri
Kansas City

Children's Mercy Hospital

Kathleen Neville, MD
Principal Investigator

New York
New York

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Julia L. Glade-Bender
Principal Investigator

NYU Cancer Institute at New York University Medical Center

Elizabeth A. Raetz
Principal Investigator

North Carolina
Charlotte

Levine Children's Hospital

Javier Oesterheld, MD

Javier Oesterheld, MD
Principal Investigator

Ohio
Cleveland

Rainbow Babies

Joe Matloub, MD

Tennessee
Memphis

St. Jude Children's Research Hospital

Deepa Bhojwani, MD

Texas
Fort Worth

Cook Children's Hospital

Ken Heym, MD

Utah
Salt Lake City

Primary Children's Medical Center

Elizabeth Raetz, MD

Washington
Seattle

Children's Hospital and Regional Medical Center - Seattle

Blythe Thompson, MD
Principal Investigator

Wisconsin
Milwaukee

Medical College of Wisconsin Cancer Center

Mike Burke, MD

Austria

Vienna

St. Anna Children's Hospital

Andische Attarbaschi, MD, PhD

Canada

Quebec
Montreal

Sainte Justine University Hospital

Henrique Bittencourt, MD

France

Lille

CHU Lille

Brigitte Nelken, MD, Phd

Italy

Rome

Bambino Gesù Hospital

Franco Locatelli, MD, PhD

Netherlands

Rotterdam

Erasmus MC - Sophia

Michel Zwaan, MD, PhD

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00981799
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.