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Talotrexin in Treating Young Patients With Recurrent Solid Tumors or Leukemia That is Recurrent or Does Not Respond to Treatment

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: NCT00458744
Recruitment Status : Withdrawn (Study withdrawn because of toxicity reported on the adult phase 1 trial.)
First Posted : April 11, 2007
Last Update Posted : August 8, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE April 9, 2007
First Posted Date  ICMJE April 11, 2007
Last Update Posted Date August 8, 2014
Study Start Date  ICMJE February 2007
Estimated Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2007)
  • Maximum tolerated dose of talotrexin
  • Toxicity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00458744 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2007)
  • Antitumor activity
  • Tolerability
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 Talotrexin in Treating Young Patients With Recurrent Solid Tumors or Leukemia That is Recurrent or Does Not Respond to Treatment
Official Title  ICMJE A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of talotrexin in treating young patients with recurrent solid tumors or leukemia that is recurrent or does not respond to treatment.

Detailed Description



  • Estimate the maximum tolerated dose (MTD) and recommended phase II dose of talotrexin in younger patients with recurrent solid tumors or recurrent or refractory leukemia.
  • Determine the toxicity of this drug in these patients.


  • Determine the antitumor activity of this drug in these patients.
  • Assess the tolerability of the defined MTD of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (solid tumor vs leukemia).

  • Stratum 1 (recurrent solid tumor): Patients receive talotrexin IV over 10 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of talotrexin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).

  • Stratum 2 (recurrent or refractory leukemia): A cohort of 3-6 patients with leukemia receive treatment as in stratum 1 at the MTD determined in stratum 1. If 2 or 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, accrual is stopped.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Brain and Central Nervous System Tumors
  • Leukemia
  • Lymphoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: talotrexin
  • Procedure: chemotherapy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 7, 2014)
Original Enrollment  ICMJE
 (submitted: April 9, 2007)
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • Diagnosis of either of the following:

    • Recurrent solid tumor

      • Histologically confirmed* malignancy at original diagnosis or relapse
      • Measurable or evaluable disease
      • Lymphoma or primary CNS tumor allowed

        • Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for the past 7 days
    • Recurrent or refractory leukemia

      • Confirmed relapse, as defined by M3 marrow (25% blasts in bone marrow aspirate or biopsy)
      • Active extramedullary disease allowed provided there is no leptomeningeal involvement NOTE: *Histological confirmation not required for intrinsic brain stem tumors
  • Bone marrow metastases allowed

    • Not refractory to red blood cell or platelet transfusion
  • No pleural effusion or significant ascites
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
  • No Down syndrome


  • Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) OR Lansky PS 50-100% (for patients ≤ 10 years of age)
  • Absolute neutrophil count ≥ 1,000/mm³ (for patients with solid tumors without bone marrow involvement)
  • Platelet count ≥ 100,000/mm³ (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine adjusted according to age as follows:

    • No greater than 0.6 mg/dL (1 year to 23 months)
    • No greater than 0.8 mg/dL (2 to 5 years)
    • No greater than 1.0 mg/dL (6 to 9 years)
    • No greater than 1.2 mg/dL (10 to 12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male])
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 110 U/L (ULN is 45 U/L)
  • Albumin ≥ 2 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No known condition that, in the opinion of the investigator, would preclude study compliance


  • Recovered from all prior treatment-related toxicity
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) (for patients with solid tumors)
  • At least 24 hours since prior cytoreduction therapy initiated with hydroxyurea (for patients with leukemia)
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or ≥ 50% radiotherapy to the pelvis
  • At least 6 weeks since prior substantial bone marrow radiotherapy
  • At least 3 months since prior stem cell transplant or rescue without TBI

    • No evidence of active graft-versus-host disease
  • At least 7 days since prior growth factor therapy
  • At least 7 days since prior biological therapy
  • No nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin or other salicylates, penicillins, sulfa drugs (bactrim, septra), ciprofloxacin, tetracycline, thiazide diuretics, or probenecid within 2 days prior to, during, or within 5 days after treatment with talotrexin
  • No long-acting NSAIDs (e.g., nabumetone, naproxen, oxaprozin, piroxicam) within 5 days prior to, during, or within 5 days after treatment with talotrexin
  • No concurrent investigational drugs
  • No concurrent anticancer agents or therapy (e.g., chemotherapy, radiotherapy, immunotherapy, or biologic therapy)
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 Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00458744
Other Study ID Numbers  ICMJE ADVL0613
COG-ADVL0613 ( Other Identifier: Children's Oncology Group )
CDR0000538359 ( Other Identifier: Clinical )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: James Croop, MD, PhD Riley's Children Cancer Center at Riley Hospital for Children
Study Chair: Sultan Ahmed Pradhan, MD Tata Memorial Hospital
PRS Account Children's Oncology Group
Verification Date August 2014

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