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Phase I Study of UCN-01 and Cytarabine (ARA-C) in Patients With Acute Myelogenous Leukemia, and Myelodysplastic Syndromes

Phase 1
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

Phase I Study of UCN-01 and Cytarabine (ARA-C) in Patients With Acute Myelogenous Leukemia, and Myelodysplastic Syndromes

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.

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.

Inclusion Criteria:

1. 1. Patients with refractory or relapsed acute myelogenous leukemia, or
myelodysplastic syndromes (RAEB or RAEB-T).

2. 2. Performance status of =< 2

3. 3. Signed informed consent indicating that patients are aware of the investigational
nature of this study in keeping with the policies of the hospital. The only
acceptable consent form is the one attached at the end of this protocol for each
participating institution.

4. 4. Patients must have been off chemotherapy for 2 weeks prior to entering this study
and recovered from the toxic effects of that therapy, unless there is evidence of
rapidly progressive disease.

5. 5. Bilirubin and creatinine (or creatinine clearance) should be within institutional
normal limits.

6. 6. Patients must have relapsed or failed to respond after high-dose ara-C-based
(>=1g/m2/day x 3 days) chemotherapy.

7. 7. Corrected DLCO >50%.

8. 8. Patients with >=3 cardiac risk factors (smoking, hypertension, family history of
coronary artery disease, diabetes mellitus, hypercholesterolemia) should have a
nuclear medicine stress test.

Exclusion Criteria:

1. 1. The anti-proliferative activity of the experimental drug may be harmful to the
developing fetus or nursing infant. Therefore, pregnant and nursing females will be
excluded. Patients of childbearing potential should practice effective methods of

2. 2. Patients who are eligible for allogeneic marrow transplant and who have a donor
will be offered transplant.

3. 3. Patients with existing pulmonary diseases, history of coronary artery disease or
who have received radiotherapy to the mediastinum.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) Cytarabine + UCN-01

Outcome Time Frame:

4 week cycle

Safety Issue:


Principal Investigator

Jorge Cortes, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Federal Government

Study ID:




Start Date:

December 1999

Completion Date:

January 2007

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • recurrent adult acute myeloid leukemia
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • previously treated myelodysplastic syndromes
  • childhood myelodysplastic syndromes
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • cytarabine
  • 7-hydroxystaurosporine
  • UCN-01
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
Arthur G. James Cancer Hospital - Ohio State University Columbus, Ohio  43210