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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00981799
Recruitment Status : Terminated (Slow accrual rate)
First Posted : September 22, 2009
Last Update Posted : November 24, 2015
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium

Brief 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.

Condition or disease Intervention/treatment Phase
Relapsed T-Cell Acute Lymphoblastic Leukemia Relapsed T-Cell Lymphoblastic Lymphoma Drug: Nelarabine Drug: Etoposide Drug: Cyclophosphamide Drug: Methotrexate Drug: Filgrastim Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC
Study Start Date : June 2010
Actual Primary Completion Date : November 2015

Intervention Details:
  • Drug: Nelarabine
    Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.
    Other Names:
    • Arranon
    • Compound 506U78
  • Drug: Etoposide
    100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5
    Other Names:
    • VePesid
    • Etopophos
    • VP-16
  • Drug: Cyclophosphamide
    Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.
    Other Name: Cytoxan
  • Drug: Methotrexate

    Give between day 29 and 36 or when ANC>750 and PLTS>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.

    Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but <2 years of age 10 mg for patients age greater than or equal to 2, but <3 years of age 12 mg for patients greater than or equal to 3, but < 9 years of age 15 mg for patients greater than or equal to >9 years of age

    Other Names:
    • MTX
    • Amethopterin
    • Trexall
  • Drug: Filgrastim
    5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is > 1000/mm3 for two consecutive days.
    Other Names:
    • Neupogen
    • GCSF
    • granulocyte colony stimulating factor

Primary Outcome Measures :
  1. To determine the maximum tolerated doses and dose-limiting toxicities (DLTs) of nelarabine, etoposide and cyclophosphamide when given in combination to children with T-ALL and bone marrow relapse or T-LL. [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. To determine the complete remission rate after 1 and 2 courses of this therapy in children with T-ALL and bone marrow relapse or T-LL. [ Time Frame: 1-3 months ]
  2. To determine the percent of children with T-ALL and 1st BM relapse that have a complete response after therapy on this study and proceed to stem cell transplantation in complete response within 20 weeks of beginning this regimen. [ Time Frame: 5 months ]
  3. To determine minimal residual disease (MRD) levels at the end of each course of treatment. [ Time Frame: 60 days ]
  4. To evaluate the vitamin B12 pathway and metabolites and the potential association of neurotoxicity following nelarabine therapy with alterations in this pathway. [ Time Frame: 3 years ]
  5. To determine, in a preliminary manner, whether patients with relapsed T-ALL/LL have a distinct signaling signature that distinguishes malignant cells from normal thymocytes. [ Time Frame: 3 years ]
  6. To evaluate, in a preliminary manner, whether phospho-flow cytometry can be used to predict clinical response to Nelarabine. [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00981799

  Hide Study Locations
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United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Orange County
Orange, California, United States
UCSF School of Medicine
San Francisco, California, United States, 94143-0106
United States, Colorado
The Children's Hospital, University of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States
United States, Florida
University of Miami Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States
United States, Illinois
Lurie Children's Hospital
Chicago, Illinois, United States
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States
United States, Massachusetts
Dana Farber
Boston, Massachusetts, United States
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0914
United States, Minnesota
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404-4597
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, New York
New York University Medical Center
New York, New York, United States, 10016
Children's Hospital New York-Presbyterian
New York, New York, United States, 10032
United States, North Carolina
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Ohio
Rainbow Babies
Cleveland, Ohio, United States
Nationwide Childrens Hospital
Columbus, Ohio, United States
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, Tennessee
St. Jude
Memphis, Tennessee, United States, 38105-3678
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
United States, Texas
University of Texas at Southwestern
Dallas, Texas, United States
Cook Children's Hospital
Fort Worth, Texas, United States
United States, Utah
Primary Children's
Salt Lake City, Utah, United States
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Australia, Queensland
Royal Children's Hospital
Brisbane, Queensland, Australia
Australia, Victoria
Royal Children's Hospital, Melbourne
Melbourne, Victoria, Australia
Sydney Children's Hospital
Sydney, Australia
Children's Hospital at Westmead
Westmead, NSW, Australia
St. Anna Children's Hospital
Vienna, Austria
Canada, Ontario
Hospital for Sick Kids
Toronto, Ontario, Canada
Canada, Quebec
Sainte Justine University Hospital
Montreal, Quebec, Canada
British Columbia Children's Hospital
Vancouver, Canada
CHU Lille
Lille, France
Bambino Gesù Hospital
Rome, Italy
Erasmus MC - Sophia
Rotterdam, Netherlands
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
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Study Chair: Jim Whitlock, MD The Hospital for Sick Children

Additional Information:
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Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium Identifier: NCT00981799     History of Changes
Other Study ID Numbers: T2008-002
First Posted: September 22, 2009    Key Record Dates
Last Update Posted: November 24, 2015
Last Verified: November 2015
Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:
T cell
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Dermatologic Agents
Enzyme Inhibitors