5-Fluoro-2-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

2014-08-27 03:16:58 | BioPortfolio


RATIONALE: 5-Fluoro-2'-deoxycytidine (FdCyd) may inhibit cancer cell growth by increasing the production in cells of compounds that suppress growth or by otherwise killing cells. Although FdCyd is stable as a drug solution, it is rapidly inactivated by an enzyme present in people. Tetrahydrouridine (THU) is included in the treatment to inhibit the enzyme, prolonging the time FdCyd remains in the body.

PURPOSE: This randomized phase II trial is studying two different schedules of FdCyd to compare how well they work when given together with THU in treating patients with acute myeloid leukemia or myelodysplastic syndromes.



I. Conduct a safety lead-in to refine the dose of FdCyd to be used in patients with Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) on each of two schedules (see Treatment Schema) to be used in the Phase II portion of the protocol.

II. To determine the anti-tumor activity of FdCyd and THU on two different schedules, as assessed by the objective response rate.

III. Evaluate time to treatment failure and survival in subjects with relapsed/refractory AML, relapsed/refractory or newly diagnosed MDS at int-1 or greater, or newly diagnosed AML patients over the age of 60.

IV. Evaluate whether treatment with FdCyd and THU alters DNA methylation patterns in peripheral blood mononuclear cells, including malignant myeloid cells, by analysis of LINE-1 methylation.

V. Determine the ratio of gamma to beta-globin mRNA by RT-PCR in blood cells before and after therapy as a marker of drug effect.

VI. To determine the changes in cytokines in the circulating blood and marrow before and after treatment with FdCyd and THU.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive FdCyd IV over 3 hours and THU IV over 3 hours on days 1-5 and 15-19. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive FdCyd IV over 3 hours and THU IV over 3 hours on days 1-5 and 8-12. Courses repeat every 21days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Adult Acute Myeloid Leukemia


5-fluoro-2-deoxycytidine, tetrahydrouridine, laboratory biomarker analysis, reverse transcriptase-polymerase chain reaction, DNA methylation analysis


City of Hope
United States




City of Hope Medical Center

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:16:58-0400

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