Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	1 to 21	NCI	COG-ADVL0411 ADVL0411, NCT00083070

Objectives

Primary

1. Determine the maximum tolerated dose and recommended phase II dose of temozolomide in pediatric patients with refractory or recurrent leukemia.
2. Determine the toxic effects of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.

Secondary

1. Determine the antitumor activity of this drug in these patients.
2. Determine the biologic activity and mechanism(s) of resistance to this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed leukemia of any of the following types:
  • Acute lymphoblastic leukemia
  • Acute myeloid leukemia
  • Chronic myelogenous leukemia in blast crisis



• Refractory or recurrent disease



• Immunophenotypic confirmation of disease at initial diagnosis or recurrence



• More than 25% blasts in the bone marrow (M3)



• Active extramedullary disease allowed except for leptomeningeal disease



• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life



• No active CNS disease

Prior/Concurrent Therapy:

Biologic therapy

• At least 7 days since prior biologic therapy, including immunotherapy
• At least 3 months since prior stem cell transplantation
  • No evidence of active graft-vs-host disease
• No concurrent biologic therapy
• No concurrent immunotherapy

Chemotherapy

• Recovered from prior chemotherapy
• At least 6 weeks since prior nitrosoureas
• Prior therapy with hydroxyurea allowed for up to 24 hours before initiation of study drug
• No other concurrent chemotherapy

Endocrine therapy

• Concurrent hydrocortisone or other corticosteroids allowed as premedications prior to blood product transfusions in patients with prior severe allergic reactions

Radiotherapy

• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent anticancer agents
• No other concurrent investigational drugs

Patient Characteristics:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (for patients > 10 years of age)
• Lansky 50-100% (for patients ≤ 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• WBC < 30,000/mm³ (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator)
• Platelet count ≥ 20,000/mm³ (platelet transfusions allowed)
• Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)

Hepatic

• ALT ≤ 5 times upper limit of normal (ULN)
• Albumin ≥ 2 g/dL
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine normal for age

  OR

• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m²

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

Expected Enrollment

A total of 3-36 patients will be accrued for this study within 18-24 months.

Outcomes

Maximum tolerated dose and recommended phase II dose
Toxicity as assessed by CTCAE 3.0
Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½)

Antitumor activity
Biologic activity and mechanisms of resistance

Outline

This is an open-label, dose-escalation, multicenter study.

Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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

Horton TM, Thompson PA, Berg SL, et al.: Phase I pharmacokinetic and pharmacodynamic study of temozolomide in pediatric patients with refractory or recurrent leukemia: a Children's Oncology Group Study. J Clin Oncol 25 (31): 4922-8, 2007.[PUBMED Abstract]

Horton TM, Dolan E, Hegde M, et al.: A phase I study of temozolomide (Temodar®) in pediatric patients with relapsed or refractory leukemia: a Children's Oncology Group study. [Abstract] Blood 106 (11): A-4455, 2005.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Terzah Horton, MD, PhD, Protocol chair		Ph: 832-824-4269 Email: tmhorton@txccc.org

Registry Information
Official Title		A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias
Trial Start Date		2004-03-22
Registered in ClinicalTrials.gov		NCT00083070
Date Submitted to PDQ		2004-03-17
Information Last Verified		2006-03-08
NCI Grant/Contract Number		CA97452

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