Working… Menu
Help guide our efforts to modernize
Send us your comments by March 14, 2020.

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Recruitment Status : Withdrawn (Study withdrawn because of toxicity reported on the adult phase 1 trial.)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

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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Leukemia Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific Drug: talotrexin Procedure: chemotherapy Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Primary Purpose: Treatment
Official Title: A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias
Study Start Date : February 2007
Estimated Primary Completion Date : July 2008

Primary Outcome Measures :
  1. Maximum tolerated dose of talotrexin
  2. Toxicity

Secondary Outcome Measures :
  1. Antitumor activity
  2. Tolerability

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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


  • 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)

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): NCT00458744

Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Layout table for investigator information
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

Layout table for additonal information
Responsible Party: Children's Oncology Group Identifier: NCT00458744    
Other Study ID Numbers: ADVL0613
COG-ADVL0613 ( Other Identifier: Children's Oncology Group )
CDR0000538359 ( Other Identifier: Clinical )
First Posted: April 11, 2007    Key Record Dates
Last Update Posted: August 8, 2014
Last Verified: August 2014
Keywords provided by Children's Oncology Group:
juvenile myelomonocytic leukemia
relapsing chronic myelogenous leukemia
unspecified childhood solid tumor, protocol specific
childhood chronic myelogenous leukemia
childhood acute promyelocytic leukemia (M3)
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood infratentorial ependymoma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood supratentorial ependymoma
recurrent childhood brain stem glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumors
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway glioma
high-grade childhood cerebral astrocytoma
low-grade childhood cerebral astrocytoma
recurrent childhood brain tumor
childhood spinal cord tumor
recurrent/refractory childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
recurrent childhood large cell lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases