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

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ClinicalTrials.gov Identifier: NCT00004263
Recruitment Status : Completed
First Posted : July 26, 2004
Last Update Posted : July 30, 2012
Information provided by (Responsible Party):

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  (Clinical Trial)
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 : December 1999
Primary Completion Date : January 2007
Study Completion Date : January 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

Outcome Measures

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) Cytarabine + UCN-01 [ Time Frame: 4 week cycle ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 contraception.
  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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004263

United States, Ohio
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio, United States, 43210
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study Chair: Jorge Cortes, MD M.D. Anderson Cancer Center
More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00004263     History of Changes
Other Study ID Numbers: DM99-165
U01CA062461 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
MDA-DM-99165 ( Other Identifier: NCI PDQ/UT MD Anderson Cancer Center )
CDR0000067522 ( Registry Identifier: NCI PDQ )
First Posted: July 26, 2004    Key Record Dates
Last Update Posted: July 30, 2012
Last Verified: July 2012

Keywords provided by M.D. Anderson Cancer Center:
recurrent adult acute myeloid leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
previously treated myelodysplastic syndromes
childhood myelodysplastic syndromes
Cytosine arabinosine hydrochloride

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors