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 MDSTo 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
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