STI571 in Treating Patients With Recurrent Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Study of STI571 in Ph+ Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 260 mg/m2 imatinib mesylate (ST571)<br> | Drug: imatinib mesylate<br> <br> * Other names: IND # 55666;|
| Experimental: 340 mg/m2 imatinib mesylate (ST571)<br> | Drug: imatinib mesylate<br> <br> * Other names: IND # 55666;|
| Experimental: 440 mg/m2 imatinib mesylate (ST571)<br> | Drug: imatinib mesylate<br> <br> * Other names: IND # 55666;|
| Experimental: 570 mg/m2 imatinib mesylate (ST571)<br> | Drug: imatinib mesylate<br> <br> * Other names: IND # 55666;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | To estimate the maximum tolerated dose (MTD) of STI571 administered orally once daily without interruption to children with recurrent Ph+ leukemia. | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities | To determine the dose-limiting toxicities (DLT) of STI571 given on this schedule. | Length of study | 
| Characterize the pharmacokinetic behavior | To characterize the pharmacokinetic behavior of STI571 in children with recurrent Ph+ leukemia. | Length of study | 
| Define the anti-leukemic activity of STI571 | To preliminarily define the anti-leukemic activity of STI571 within the confines of a Phase I study. | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, relapsing chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive, childhood chronic myelogenous leukemia