Clinical trial NCT00083070: Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia
Official title: A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
relapsing chronic myelogenous leukemia
childhood acute promyelocytic leukemia (M3)
blastic phase chronic myelogenous leukemia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-17
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide in treating young patients with refractory or recurrent leukemia.

Detailed description: OBJECTIVES:

Primary

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

Secondary

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

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.

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

Eligibility 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

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/mm\^3 (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator)
* Platelet count ≥ 20,000/mm\^3 (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 m\^2

Other

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

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

Primary outcomes:
measure: Maximum tolerated dose and recommended phase II dose
measure: Toxicity as assessed by CTCAE 3.0
measure: Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½)
Secondary outcomes:
measure: Antitumor activity
measure: Biologic activity and mechanisms of resistance
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Minneapolis
country: United States
facility: Fairview University Medical Center - University Campus
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: Texas Children's Cancer Center
name: Terzah M. Horton, MD, PhD
role: STUDY_CHAIR
References:
citation: Horton TM, Thompson PA, Berg SL, Adamson PC, Ingle AM, Dolan ME, Delaney SM, Hedge M, Weiss HL, Wu MF, Blaney SM; Children's Oncology Group Study. 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. 2007 Nov 1;25(31):4922-8. doi: 10.1200/JCO.2007.12.0667.
citation: 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.