STI571 in Treating Patients With Recurrent Leukemia

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Leukemia

Treatments: Drug: imatinib mesylate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00004932

COG-P9973 (Other Identifier)

P9973

POG-9973 (Other Identifier)

CCG-P9973 (Other Identifier)

CDR0000067616 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Imatinib mesylate may interfere with the growth of cancer cells and may be an effective treatment for leukemia.

PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent leukemia.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with recurrent Philadelphia chromosome-positive leukemia.
• Characterize the pharmacokinetic behavior of this drug in this patient population.
• Determine preliminarily the antileukemic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral imatinib mesylate (STI571) once daily for 28 days. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of STI571 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 32 patients will be accrued for this study within 3.5 years.

Enrollment: 31 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Recurrent Philadelphia (Ph) chromosome-positive leukemia

  • Recurrent or refractory acute lymphoblastic or myeloblastic leukemia OR

  • Chronic myelogenous leukemia with resistance to interferon alfa with any of the following:

    • WBC at least 20,000/mm^3 after at least 3 months of interferon therapy
    • At least 100% increase in WBC to at least 20,000/mm^3 confirmed over 2 weeks while receiving interferon alfa
    • At least 66% Ph chromosome-positive cells after 1 year of interferon therapy
    • At least 30% increase in number of Ph chromosome-positive cells after an interferon-induced response while continuing interferon therapy

PATIENT CHARACTERISTICS:

Age:

• Under 22

Performance status:

• Karnofsky 50-100% if over 10 years of age OR
• Lansky 50-100% if 10 years of age and under

Life expectancy:

• At least 8 weeks

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGPT less than 3 times normal
• Albumin greater than 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• If prior allogeneic stem cell transplantation, no uncontrolled graft-versus -host disease
• No seizure disorder if on anticonvulsants
• No uncontrolled infection
• No CNS toxicity greater than grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 1 week since prior biologic therapy and recovered
• At least 3 months since prior stem cell transplantation (SCT)
• At least 1 week since prior growth factors
• At least 1 week since prior interferon alfa

Chemotherapy:

• Recovered from prior chemotherapy
• At least 6 weeks since prior busulfan and nitrosoureas
• At least 2 weeks since prior homoharringtonine
• At least 1 week since low-dose cytarabine
• At least 2 weeks since prior moderate-dose cytarabine
• At least 4 weeks since prior high-dose cytarabine
• At least 3 weeks since all other prior cytotoxic chemotherapies
• No prior hydroxyurea

Endocrine therapy:

• Must be on a stable dose of steroids if received prior allogeneic SCT

Radiotherapy:

• Recovered from prior radiotherapy
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 6 months since prior craniospinal radiotherapy
• At least 6 months since prior radiotherapy to 50% or more of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational agents
• No concurrent anticonvulsants

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 4 patient groups

260 mg/m2 imatinib mesylate (ST571)

Experimental group

Treatment:

Drug: imatinib mesylate

340 mg/m2 imatinib mesylate (ST571)

Experimental group

Treatment:

Drug: imatinib mesylate

440 mg/m2 imatinib mesylate (ST571)

Experimental group

Treatment:

Drug: imatinib mesylate

570 mg/m2 imatinib mesylate (ST571)

Experimental group

Treatment:

Drug: imatinib mesylate