RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. UCN-01 may make cancer cells more sensitive to cytarabine.

PURPOSE: Phase I trial to study the effectiveness of cytarabine and UCN-01 in treating patients who have refractory or relapsed acute myelogenous leukemia or myelodysplastic syndrome.

Condition	Treatment or Intervention	Phase
recurrent adult acute myeloid leukemia refractory anemia with excess blasts in transformation Previously Treated Myelodysplastic Syndrome secondary myelodysplastic syndrome de novo myelodysplastic syndrome refractory anemia with excess blasts	Drug: cytarabine  Drug: UCN-01	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of cytarabine when combined with UCN-01 in patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndrome.

II. Determine the dose limiting toxicity, pharmacokinetics, and pharmacodynamics of this regimen in these patients.

III. Assess the antileukemia effect of this regimen in this patient population.

PROTOCOL OUTLINE: This is a dose escalation, multicenter study of cytarabine.

Patients receive cytarabine IV over 24 hours on days 1-4 of each course. Patients receive UCN-01 IV over 24 hours on days 2-4 of course 1 and over 36 hours beginning on day 2 of subsequent courses. Treatment repeats every 4 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven refractory or relapsed acute myelogenous leukemia or myelodysplastic syndrome (refractory anemia with excess blasts [RAEB] or RAEB in transformation)
• Relapse or failure to respond after high dose cytarabine (greater than 1 g/m2/day for 3 days) based chemotherapy
• Ineligible for allogeneic bone marrow transplantation

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; At least 24 hours since prior hydroxyurea for rapidly proliferative disease; At least 2 weeks since other prior chemotherapy (unless there is evidence of rapidly progressive disease) and recovered
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: Not specified
• Performance status: 0-2
• Life expectancy: Not specified
• Hematopoietic: Peripheral blood circulating blasts at least 2,000/mm3
• Hepatic: Bilirubin normal
• Renal: Creatinine normal OR Creatinine clearance normal
• Other: Not pregnant or nursing; Fertile patients must use effective contraception

Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Jorge Cortes,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000067522; MDA-DM-99165; NCI-T99-0100
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004263
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08