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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Therapeutic Advances in Childhood Leukemia Consortium
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier:
NCT00981799
First received: September 9, 2009
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Therapeutic Advances in Childhood Leukemia Consortium:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To determine minimal residual disease (MRD) levels at the end of each course of treatment. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate, in a preliminary manner, whether phospho-flow cytometry can be used to predict clinical response to Nelarabine. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: June 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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
  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have first relapse T-cell ALL or T-cell lymphoblastic lymphoma.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00981799

Contacts
Contact: Jeannette van der Giessen, BA 323-361-8725 jvandergiessen@chla.usc.edu
Contact: Elena Eckroth 323-361-5429 eeckroth@chla.usc.edu

  Show 24 Study Locations
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
GlaxoSmithKline
Investigators
Study Chair: Jim Whitlock, MD The Hospital for Sick Children
  More Information

Additional Information:
No publications provided

Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier: NCT00981799     History of Changes
Other Study ID Numbers: T2008-002
Study First Received: September 9, 2009
Last Updated: January 31, 2014
Health Authority: United States: Institutional Review Board
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Brazil: National Committee of Ethics in Research

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:
Relapse
T cell
Lymphoblastic
Leukemia
Lymphoma
Nelarabine
TACL
NECTAR

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Etoposide
Etoposide phosphate
Lenograstim
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Adjuvants, Immunologic
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on November 27, 2014