Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: STI571 in Treating Patients With Recurrent Leukemia

Summary: 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: 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.

Eligibility: 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

Relevance to patient case: not relevant