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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00004263
First received: January 28, 2000
Last updated: July 27, 2012
Last verified: July 2012

January 28, 2000
July 27, 2012
December 1999
January 2007   (final data collection date for primary outcome measure)
Maximum Tolerated Dose (MTD) Cytarabine + UCN-01 [ Time Frame: 4 week cycle ] [ Designated as safety issue: Yes ]
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Complete list of historical versions of study NCT00004263 on ClinicalTrials.gov Archive Site
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Cytarabine and UCN-01 in Treating Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Phase I Study of UCN-01 and Cytarabine (ARA-C) in Patients With Acute Myelogenous Leukemia, and Myelodysplastic Syndromes

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • 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
Experimental: Cytarabine + UCN-01
Interventions:
  • Drug: 7-hydroxystaurosporine (UCN-01)
  • Drug: Cytarabine (Ara-C)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
January 2007
January 2007   (final data collection date for primary outcome measure)

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.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00004263
DM99-165, U01CA062461, P30CA016672, MDA-DM-99165, NCI-T99-0100, CDR0000067522
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study Chair: Jorge Cortes, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP