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A Phase I Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) in Myeloid Leukemia and MDS

Phase 1
18 Years
Open (Enrolling)
Adult Acute Myeloid Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Untreated Adult Acute Myeloid Leukemia

Thank you

Trial Information

A Phase I Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) in Myeloid Leukemia and MDS

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of FdCyd administered with a fixed
dose of THU in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome
(MDS), once daily on days 1-10 of a 21-day treatment cycle. II. To describe the toxicities
of FdCyd/THU in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome
(MDS). III. To document all clinical responses and hematologic improvement in patients
treated with FdCyd/THU. IV. To obtain preliminary information regarding the effect of
FdCyd/THU on deoxyribonucleic acid (DNA) methylation patterns in peripheral blood
mononuclear cells and bone marrow aspirates, including malignant myeloid cells; the ratio of
gamma- to beta-globin messenger ribonucleic acid (mRNA) in blood cells; and serum cytokines.
OUTLINE: This is a dose-escalation study of FdCyd. Patients receive FdCyd intravenously (IV)
over 3 hours and THU IV over 3 hours on days 1-10. Courses repeat every 21days in the
absence of disease progression or unacceptable toxicity. After completion of study
treatment, patients are followed up for 4 weeks.

Inclusion Criteria:

Patients must have the following diagnosis:

- Acute myeloid leukemia

- Relapsed or refractory

- Newly diagnosed in patients age 60 and above or of any age unable to receive
standard induction regimen

- Patients with MDS with an International Prognostic Scoring System (IPSS) score >= 0.5

- Newly diagnosed

- Relapsed or refractory

- Any prior therapy must have been completed >= 2 weeks prior to enrollment and the
participant must have recovered to eligibility levels from prior toxicity

- No limit to number of prior regimens

- Hydroxyurea is allowed prior to enrollment to keep white blood cell count (WBC) below
20 K

- Valproic acid not being used for seizure control should be stopped 72 hours before
starting therapy

- Prior therapy with hypomethylating agent (decitabine or azacitidine) is allowed and
must be completed >= 6 weeks prior to enrollment

- Relapsed patients are eligible post allogeneic or matched unrelated donor (MUD)
transplant after 100 days; there should be no active acute graft versus host disease
of any grade and patient should not be receiving immunosuppression for acute graft
versus host disease; the patient must not have Chronic Graft versus Host disease
(cGvHD) other than mild skin, oral, or ocular cGvHD not requiring systemic

- Relapsed patients are eligible post autologous transplant after 100 days post
transplant, with recovery of their counts absolute neutrophil count (ANC) > 1000 and
platelets greater than 75K at some point post transplant

- Karnofsky performance status >= 60%

- Total bilirubin < 1.5 x institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
=< 2.5 x institutional upper limit of normal

- Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60
mL/min for patients with creatinine levels above 1.5 x institutional upper limit of

- Pregnant women will be excluded from this trial; nursing women are also excluded;
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) for the duration of study
participation, and for 3 months after completion of study; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

- Patients should not be receiving any other investigational agents

Exclusion Criteria:

- Patients with clinically significant illnesses which would compromise participation
in the study, including, but not limited to: active or uncontrolled infection, immune
deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection,
active Hepatitis B, active Hepatitis C, or uncontrolled diabetes, uncontrolled
hypertension, symptomatic congestive heart failure, unstable angina pectoris,
myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia; or
psychiatric illness/social situations that would limit compliance with study

- Patients with additional (other than AML/MDS) currently active primary malignancy
other than curatively treated carcinoma in situ (CIS) of the cervix, or basal or
squamous cell carcinoma of the skin; patients are not considered to have a "currently
active" malignancy if they have completed therapy for a prior malignancy and disease
free from prior malignancies for > 2 years

- Patients with active central nervous system (CNS) disease; these patients are
excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation
of neurologic and other adverse events

- Active infections, including opportunistic following allo, MUD, or auto transplant
(including but not limited to cytomegalovirus [CMV], fungal infection etc)

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD and dose-limiting toxicity (DLT) of the new 10-day schedule of FdCyd/THU

Outcome Description:

Toxicities will be summarized by Common Terminology Criteria for Adverse Events (CTCAE) grade and attribution using the version current at the initiation of the protocol.

Outcome Time Frame:

10 days

Safety Issue:


Principal Investigator

Robert Chen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Adult Acute Myeloid Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Untreated Adult Acute Myeloid Leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



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