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

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ClinicalTrials.gov Identifier: NCT00981799
Recruitment Status : Terminated (Slow accrual rate)
First Posted : September 22, 2009
Last Update Posted : November 24, 2015
Sponsor:
Collaborators:
GlaxoSmithKline
Novartis
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium

Tracking Information
First Submitted Date  ICMJE September 9, 2009
First Posted Date  ICMJE September 22, 2009
Last Update Posted Date November 24, 2015
Study Start Date  ICMJE June 2010
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00981799 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2009)
  • 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 ]
  • 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 ]
  • To determine minimal residual disease (MRD) levels at the end of each course of treatment. [ Time Frame: 60 days ]
  • 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 ]
  • 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 ]
  • To evaluate, in a preliminary manner, whether phospho-flow cytometry can be used to predict clinical response to Nelarabine. [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
Official Title  ICMJE A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed T-Cell Acute Lymphoblastic Leukemia
  • Relapsed T-Cell Lymphoblastic Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 20, 2015)
23
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2009)
36
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   France,   Italy,   Netherlands,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT00981799
Other Study ID Numbers  ICMJE T2008-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Therapeutic Advances in Childhood Leukemia Consortium
Study Sponsor  ICMJE Therapeutic Advances in Childhood Leukemia Consortium
Collaborators  ICMJE
  • GlaxoSmithKline
  • Novartis
Investigators  ICMJE
Study Chair: Jim Whitlock, MD The Hospital for Sick Children
PRS Account Therapeutic Advances in Childhood Leukemia Consortium
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP