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A Phase I Trial of Imatinib Mesylate (Gleevec, Formerly Known as STI571) in Combination With Daunorubicin and Cytarabine for C-kit Positive Relapsed AML

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

A Phase I Trial of Imatinib Mesylate (Gleevec, Formerly Known as STI571) in Combination With Daunorubicin and Cytarabine for C-kit Positive Relapsed AML



- Determine the maximum tolerated dose (MTD) and recommended phase II dose of imatinib
mesylate in combination with daunorubicin hydrochloride and cytarabine in patients with
relapsed acute myeloid leukemia.


- Assess the non-dose-limiting toxicities associated with this regimen in these patients.

- Determine any preliminary evidence of clinical activity of this regimen in these

OUTLINE: This is an open-label, dose-escalation study of imatinib mesylate.

Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7.
Patients also receive oral imatinib mesylate once daily beginning on day 1 and continuing
until disease progression or unacceptable toxicity. Patients with persistent leukemia on day
14 bone marrow biopsy but ≥ 50% reduction in bone marrow blasts receive 5 more days of
cytarabine and 2 more days of daunorubicin while continuing imatinib mesylate.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1
of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated
at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Inclusion Criteria


- Bone marrow biopsy confirming acute myeloid leukemia (AML)

- No M3 AML

- Patient must have relapsed to standard chemotherapy

- Patients who relapse within six months of response to treatment or those who
never responded to an anthracycline/cytarabine combination will be excluded

- At least 20% of peripheral blood or bone marrow blasts positive for c-kit

- No evidence of leptomeningeal involvement


- ECOG Performance Status 0-2

- Liver enzymes (AST and ALT) and total bilirubin ≤ 2 times upper limit of normal

- Serum creatinine ≤ 2 times upper limit of normal

- No New York Heart Association grade III or IV cardiac problems

- Defined as congestive heart failure or myocardial infraction within the past 6

- No known chronic liver disease (i.e., chronic active hepatitis and cirrhosis)

- No serious or poorly controlled medical conditions that could be exacerbated by the
treatment or would seriously complicate compliance with this study

- No other active primary malignancy unless it is not currently clinically significant
and does not require active intervention

- No history of HIV infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- No significant history of noncompliance to medical regimens or inability to grant
reliable informed consent


- Previous treatment-related toxicities should be resolved

- No other investigational agents within the past 28 days

- No chemotherapy within the past 4 weeks

- 6 weeks for nitrosourea or mitomycin C

- No major surgery within the past 4 weeks

- No concurrent use of the following drugs is allowed: ketoconazole, dilantin,
itraconazole, erythromycin, clarithromycin, dexamethasone, rifampin, tegretol,
phenobarbital, Hypericum perforatum (St. John's wort), cyclosporine, pimozide,
warfarin, certain HMG-CoA reductase inhibitors, traizolo-benzodiazepines, or
dihydropyridine calcium channel blockers

- No other concurrent anticancer agents, including chemotherapy and biologic agents

- No other concurrent investigational drugs

- Concurrent medications known to be metabolized by cytochrome p450 enzymes are allowed

- No therapeutic anticoagulation with warfarin will be permitted in patients
participating in this study

- Therapeutic anticoagulation may be accomplished using low-molecular weight

- Mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed

- No concurrent routine use of systemic corticosteroid therapy

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of imatinib mesylate at one year

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Anjali Advani, MD

Investigator Role:

Study Chair

Investigator Affiliation:

The Cleveland Clinic


United States: Federal Government

Study ID:




Start Date:

July 2003

Completion Date:

August 2011

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myelomonocytic leukemia (M4)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195