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

• ClinicalTrials.gov Identifier: NCT00458744
• Recruitment Status: Withdrawn
• First Posted: April 11, 2007
• Last Update Posted: August 8, 2014
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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:

OBJECTIVES:

Primary

• 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.

Secondary

• 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 Design

• 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

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose of talotrexin
2. Toxicity

Secondary Outcome Measures :

1. Antitumor activity
2. Tolerability

Eligibility Criteria

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

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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)

Contacts and Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• 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

More Information

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00458744 History of Changes
• Other Study ID Numbers: ADVL0613; COG-ADVL0613 ( Other Identifier: Children's Oncology Group ); CDR0000538359 ( Other Identifier: Clinical Trials.gov )
• First Posted: April 11, 2007
• 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:

Lymphoma; Leukemia; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Nervous System Diseases