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A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias


Phase 1
1 Year
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias


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.

Inclusion 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, thiaxide
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)

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of talotrexin

Safety Issue:

Yes

Principal Investigator

James Croop, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Riley's Children Cancer Center at Riley Hospital for Children

Authority:

Unspecified

Study ID:

CDR0000538359

NCT ID:

NCT00458744

Start Date:

February 2007

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Leukemia
  • Lymphoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • 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
  • stage IV childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • stage IV childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • stage IV childhood small noncleaved cell lymphoma
  • childhood grade III lymphomatoid granulomatosis
  • childhood nasal type extranodal NK/T-cell lymphoma
  • recurrent childhood grade III lymphomatoid granulomatosis
  • recurrent childhood pineoblastoma
  • Leukemia
  • Lymphoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms
  • Astrocytoma

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