Cytarabine and UCN-01 in Treating Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00004263

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: 7-hydroxystaurosporine (UCN-01) Drug: Cytarabine (Ara-C)	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 1999

Actual Primary Completion Date :

Jan 1, 2007

Actual Study Completion Date :

Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cytarabine + UCN-01	Drug: 7-hydroxystaurosporine (UCN-01) 20 mg/m2 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. Drug: Cytarabine (Ara-C) Starting dose 1 g/m2 IV over 24 hours on days 1-4 of each course. Treatment repeats every 4 weeks for a maximum of 4 courses. Other Names: ARA-C Cytosar DepoCyt Cytosine arabinosine hydrochloride

Arm

Intervention/Treatment

Experimental: Cytarabine + UCN-01

Drug: 7-hydroxystaurosporine (UCN-01)

20 mg/m2 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.

Drug: Cytarabine (Ara-C)

Starting dose 1 g/m2 IV over 24 hours on days 1-4 of each course. Treatment repeats every 4 weeks for a maximum of 4 courses.

Other Names:

ARA-C

Cytosar

DepoCyt

Cytosine arabinosine hydrochloride

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) Cytarabine + UCN-01 [4 week cycle]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Patients with refractory or relapsed acute myelogenous leukemia, or myelodysplastic syndromes (RAEB or RAEB-T).
1. Performance status of =< 2
1. 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.
1. 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.
1. Bilirubin and creatinine (or creatinine clearance) should be within institutional normal limits.
1. Patients must have relapsed or failed to respond after high-dose ara-C-based (>=1g/m2/day x 3 days) chemotherapy.
1. Corrected DLCO >50%.
1. 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. 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 contraception.
1. Patients who are eligible for allogeneic marrow transplant and who have a donor will be offered transplant.
1. Patients with existing pulmonary diseases, history of coronary artery disease or who have received radiotherapy to the mediastinum.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
2	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030