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A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients

Phase 1
18 Years
Open (Enrolling)
Myelodysplastic Syndrome

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Trial Information

A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients

The specific purpose of the study is to determine the safety, maximum tolerated dose (MTD)
and recommended Phase II dose of clofarabine in patients with MDS.

- We will start at a dose of 1 mg daily.

- We will treat a group of 3 patients with clofarabine at that dose level.

- If there are no severe side effects seen at that dose level, then the next group of 3
patients will receive a higher dose.

- Treatment of groups of 3 patients will continue at higher dose levels until severe
side-effects are noted.

- If more than 1 of the 3 patients experiences a severe side effect, dosing will be
stopped at that level.

- If only one of the three patients experience a severe side effect, then three more
patients will be treated, at that dose level and if they too experience severe side
effects, then dose escalation will be stopped and the maximum tolerated dose will be

- 10 more patients will be enrolled at the maximum tolerated dose.

- There will be up to 5 dose levels tested.

- We plan to test how much of the drugs are in the patient's blood at different times,
and the levels of certain proteins in their blood.

Inclusion Criteria:

- Provide signed written informed consent.

- Patients with MDS must have IPSS score that falls in the intermediate or high risk
disease (intermediate 1 will have to be transfusion dependent).

- Patients may have received up to two prior therapies for MDS including one
hypomethylating agent and/or a biologic agent (biologic agents include GM-CSF or
equivalent, danazol or equivalent, Sunitinib, Revlimid, ATG, or a vaccine).

- Age ≥ 18

- Have adequate renal and hepatic functions as indicated by the following laboratory

- Serum creatinine ≤ 1 mg/dL; if serum creatinine >l mg/dL, then the estimated
glomerular filtration rate (GFR) must be >50 mL/min/1.73 m2 as calculated by the
Modification of Diet in Renal Disease equation.

- Serum bilirubin ≤1.5 mg/dL x upper limit of normal (ULN)

- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x ULN

- Alkaline phosphatase ≤2.5 x ULN

- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent.

- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment.

- Male and female patients must use an effective contraceptive method during the study
and for a minimum of 6 months after study treatment.

Exclusion Criteria:

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver, or other organ system that
may place the patient at undue risk to undergo treatment.

- Active CNS disease

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment).

- Pregnant or lactating patients.

- Any significant concurrent disease, illness, or psychiatric disorder that would
compromise patient safety or compliance, interfere with consent, study participation,
follow up, or interpretation of study results.

- Have 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:

- 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.

- 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 (HN).

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

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

- Patients taking proton pump inhibitors such as omeprazole (Prilosec®), lansoprazole
(Prevacid®), or esomeprazole (Nexium®). Those who cannot stop taking these drugs
should be switched to H2 blockers such as famotidine (Pepcid®)or ranitidine

- Patients taking alternative medicines (such as herbal or botanical) are not

Type of Study:


Study Design:

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

Outcome Measure:

To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS).

Outcome Time Frame:

Up to 6 months

Safety Issue:


Principal Investigator

Wetzler Meir, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 144208



Start Date:

October 2009

Completion Date:

Related Keywords:

  • Myelodysplastic Syndrome
  • Myelodysplastic syndrome
  • Clofarabine
  • low-dose oral clofarabine
  • intermediate risk Myelodysplastic syndrome
  • high risk Myelodysplastic syndrome
  • Myelodysplastic Syndromes
  • Preleukemia



Roswell Park Cancer Institute Buffalo, New York  14263