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A Phase IIa Open-label, Dose Confirmation Study of Oral Clofarabine in Adult Patients Previously Treated for Myelodysplastic Syndromes(MDS)

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndromes, Secondary AML

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Trial Information

A Phase IIa Open-label, Dose Confirmation Study of Oral Clofarabine in Adult Patients Previously Treated for Myelodysplastic Syndromes(MDS)

Inclusion Criteria:

- Have a pathologically confirmed secondary Acute Myeloid Leukemia (following a history
of MDS) or MDS with an intermediate 1 (with marrow blasts great than or equal to 5%)
intermediate 2 or high risk score as assessed by the International Prognostic Scoring
System (IPSS) at study, entry. Patients with refractory anemia with excess blasts in
transformation (RAEB-t) recognized by the French-American-British (FAB) system, and
chronic myelomonocytic leukemia (CMML) will be allowed into the study. Pathologic
confirmation is the responsibility of the site investigator.

- Have previously treated MDS defined as follows: a.)Patients must have had at least
one, but no more than two, prior treatment regimens [A treatment regimen is defined
as any drug or drug combination administered for treatment of MDS with the intent of
inducing at least hematologic improvement (consistent with International Working
Group [IWG] criteria); Inadequate treatment, due to drug intolerance or other
factors, will still be considered a prior treatment regimen. Hematopoietic growth
factors, hydroxyurea, anti-thymocyte globulin (ATG), or supportive care measures
(e.g., blood transfusions, immunosuppressive agents, antibiotics) will not be
considered treatment regimens for the purpose of study entry.] b.)One of the
treatment regimens must have been either 5-azacytidine or decitabine. If
5-azacytidine or decitabine is given as a treatment regimen more than once, it will
be considered as 2 different treatment regimens. c.)Patients must not have been
refractory (i.e., progression of disease, or no evidence of response, while on the
treatment) to more than one prior treatment regimen (to be considered refractory to
decitabine or 5-azacitidine, patients must have received greater than or equal to 4

- Have documentation of prior transfusion requirements for the preceding 8 weeks (8
weeks prior to first dose of study drug).

- Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

- Be able to comply with study procedures and follow-up examinations.

- Have adequate renal and hepatic functions as indicated by predefined laboratory
values: a.)Total bilirubin < 1.5 x institutional Upper Limit of Normal (ULN) except
for unconjugated hyperbilirubin secondary to treatment for MDS or Gilbert's syndrome;
and b.)Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) < 2.5 x ULN;
and c.)Serum creatine < 1.0 mg/dL, then the estimated glomerular filtration rate
(GFR) must be >30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal
Disease (MDRD) equation.

- Be non-fertile or agree to use birth control during the study through the end of last
treatment visit and at least 90 days after.

Exclusion Criteria:

- Have had an adjustment of dose and/or schedule of erythropoietin, granulocyte colony
stimulating factor (G-CSF) or other growth factors within 8 weeks prior to the first
dose of oral clofarabine.

- Have had any prior therapy for treatment of sAML. Hydroxyurea must not have been
received within 24 hours prior to first dose of study drug.

- Have had any other chemotherapy or any investigational therapy within four weeks of
first dose of study drug.

- Have had any prior pelvic radiotherapy.

- Have had a prior hematopoietic stem cell transplant for MDS.

- Have not recovered to < grade 2 from any drug-related non-hematologic toxicity prior
to first dose of the study drug.

- Have an uncontrolled systemic fungal, bacterial, viral, or other infection (defined
as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment).

- Have a psychiatric disorder that would interfere with consent, study participation,
or follow-up.

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, or liver, in particular: a.)New
York Heart Association (NHA) classification stage II, III, or IV congestive heart
failure; b.)Coronary artery disease or arteriosclerotic cardiovascular disease
(angina, myocardial infraction) within 3 months of first dose of study drug; c.)Any
other primary cardiac disease that, in the opinion of the investigator, increases the
risk of ventricular arrhythmia.

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart had any prior treatment with Clofarabine.

- Have had a diagnosis of another malignancy, unless the patient has been disease-free
for at least 3 years following the completion of curative intent therapy with the
following exceptions: a.)Patients with treated non-melanoma skin cancer, in situ
carcinoma, or cervical intraepithelial neoplasia, regardless of the disease -free
duration, are eligible for this study if definitive treatment for the condition has
been completed. b.)Patients with organ-confined prostate cancer with no evidence of
recurrent or progressive disease based on prostate-specific antigen (PSA) values are
also eligible for this study if hormonal therapy has been initiated or a radical
prostatectomy has been performed.

- Have prior positive test for the Human Immunodeficiency Virus (HIV).

- Have currently active gastrointestinal disease, or prior surgery that may affect the
ability of the patient to absorb oral clofarabine.

- Participating in other concurrent investigational protocols that are not restricted
to data and/or sample collection for patient demographic and/or sample collection for
patient demographic and/or disease purposes.

- Have had prior treatment with a known nephrotoxic drug within 2 weeks of the first
dose of study drug, unless the patient has a calculated GFR >30 at 2 time points no
less than 7 days apart during the 2-week period prior to the first dose of study

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated dose of oral clofarabine (dosed daily x 5) for treatment of previously treated adult patients with MDS or secondary acute myeloid leukemia (following a history of MDS).

Outcome Time Frame:

Toxicity observed in first cycle after treatment will be used to confirm an appropriate dose

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2007

Completion Date:

June 2011

Related Keywords:

  • Myelodysplastic Syndromes
  • Secondary AML
  • Previously treated Myelodysplastic Syndromes (MDS)
  • oral clofarabine
  • Intermediate-1, Intermediate-2 and High Risk Myelodysplastic Syndromes (MDS)
  • secondary AML (with history of MDS)
  • Myelodysplastic Syndromes
  • Preleukemia



Weill Medical College of Cornell University New York, New York  10021
Cleveland Clinic Cleveland, Ohio  44195
University of Texas MD Anderson Cancer Center Houston, Texas  77030
The University of Chicago Chicago, Illinois  60637
Wake Forest University Baptist Medical Center Winston-Salem, North Carolina  27157
Baylor University Medical Center Blood Marrow Transplantation Research Dallas, Texas  75246