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A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS

Phase 1/Phase 2
19 Years
Not Enrolling
Myelodysplastic Syndromes

Thank you

Trial Information

A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS



- To determine the maximum tolerated dose (MTD) of clofarabine when administered with
low-dose cytarabine and filgrastim (G-CSF) in patients with intermediate-2 or high-risk
myelodysplastic syndromes (MDS).

- To evaluate efficacy as measured by hematologic response rates in patients who are
treated with this novel combination of drugs and who are not candidates for more
intensive treatment for intermediate-2 and high-risk MDS.


- To assess effects on quality of life of this patient population.

- To assess the time to acute myeloid leukemia transformation or death.

- To assess cytogenetic response rates.

- To assess changes in flow cytometric patterns.

OUTLINE: This is a phase I, nonrandomized, dose-escalation study of clofarabine followed by
a phase II study.

- Phase I: Patients receive clofarabine IV over 1 hour and low-dose cytarabine
subcutaneously (SC) on days 1-5. Patients also receive filgrastim (G-CSF) SC beginning
1 day prior to the start of chemotherapy and continuing through completion of
chemotherapy until blood counts recover. Treatment repeats every 6 weeks for up to 10
courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.

- Phase II: Patients receive clofarabine at the MTD, cytarabine, and G-CSF as in phase I.

Quality of life is assessed at baseline, prior to course 4, and after completion of study

Patients undergo bone marrow biopsy at baseline and prior to courses 3, 6, and 8 for
evaluation of treatment response. Bone marrow samples are analyzed for myeloblast phenotypic
expression profiles, which include the following parameters: percentage of CD34-positive
myeloblasts; antigen expression density of CD13, CD34, CD45, and CD117; and aberrant
myeloblast expression of CD4, CD11c, CD15, and CD56.

Inclusion Criteria


- Confirmed pathologic diagnosis of myelodysplastic syndromes

- International Prognostic Scoring System score of intermediate-2 or high-risk

- Failed or progressed after 1 prior FDA-approved treatment for MDS OR refused the
FDA-approved treatment

- Not a candidate for intensive or standard chemotherapy or stem cell transplantation,
as determined by the treating physician


- ECOG performance status 0-2

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT ≤ 3 times ULN

- Creatinine < 2.0 mg/dL

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No comorbidity or condition that, in the opinion of the investigator, may interfere
with the assessments and procedures of this protocol or that would decrease life
expectancy to < 3 months

- No active, serious infection not controlled by oral or IV antibiotics


- See Disease Characteristics

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of clofarabine (phase I)

Outcome Description:

Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 2 out of 6 patients experience dose limiting toxicities or the highest dose cohort, if 2 limiting toxicities are not observed at any dose cohort. These will be presented as actual rates. Dose limiting toxicity (DLT) will be defined according to oncology standards based on NCI CTC version 2 grading criteria (DLT = > grade 3 non-hematological toxicity or any > 4 hematological toxicity that persists for more than 4 weeks and in the opinion of the investigator is felt not to be due to disease).

Outcome Time Frame:

When/if 2 out of 6 patients experience dose limiting toxicity (DLT based on NCI CTC version 2 grading criteria)

Safety Issue:


Principal Investigator

Lori J. Maness, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

October 2009

Related Keywords:

  • Myelodysplastic Syndromes
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Myelodysplastic Syndromes
  • Preleukemia



UNMC Eppley Cancer Center at the University of Nebraska Medical Center Omaha, Nebraska  68198-7680