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Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients

Information source: Roswell Park Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myelodysplastic Syndrome

Intervention: Clofarabine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Roswell Park Cancer Institute

Official(s) and/or principal investigator(s):
Wetzler Meir, MD, Principal Investigator, Affiliation: Roswell Park Cancer Institute

Summary

This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS). The study agent, clofarabine, is produced by Genzyme Pharmaceuticals.

Clinical Details

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

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

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

Secondary outcome:

To determine the efficacy of Clofarabine in patients with MDS

To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment

Determine the differences in clofarabine plasma levels following clofarabine treatment

Evaluate the effect of clofarabine on DNA methylation

Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort)

Detailed description: 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 determined.

- 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

values:

- 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 (Zantac®).

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

permitted.

Locations and Contacts

Roswell Park Cancer Institute, Buffalo, New York 14263, United States
Additional Information

Starting date: October 2009
Last updated: May 8, 2014

Page last updated: August 23, 2015

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