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Clofarabine for Myelodysplastic Syndrome (MDS) Patients Who Failed Vidaza Treatment (tx)

This study is currently recruiting participants.
Study NCT00700011.   Last updated on June 17, 2008.   Information provided by Texas Oncology Cancer Center

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Descriptive Information Fields
Brief Title  Clofarabine for Myelodysplastic Syndrome (MDS) Patients Who Failed Vidaza Treatment (tx)
Official Title  A Pilot Study of IV Clofarabine for Patients With Myelodysplastic Syndrome Who Have Failed 5-Azacytidine
Brief Summary

We hypothesize that, in addition to its apoptotic effect, clofarabine induces DNA hypomethylation. If our hypothesis is correct, findings from the present proposal will not only contribute to information relating to the mechanisms of action of clofarabine but also provide the opportunity for combined epigenetic targeting of MDS using clofarabine with either another hypomethylating agent or a histone deacetylase inhibitor.

Clofarabine has demonstrated anti-cancer activity through inhibition of DNA synthesis and repair, induction of apoptosis, and possibly through other mechanisms. Numerous responses have been observed after treatment with clofarabine in heavily pre-treated relapsed/refractory patients with ALL, AML and high risk MDS.

In the present proposal, we will study the clinical and laboratory effects of 2 different dosages of clofarabine in patients who have failed the hypomethylating agent, 5-azacytidine. This study will recruit patients who have received at least six cycles of 5-azacytidine without response or whose disease has progressed or relapsed while on 5-azacytidine. The first cohort of patients will receive clofarabine 10 mg/m2/day for five days and the second cohort of patients 15 mg/m2/day for five days, both every four to six weeks. We will determine the frequency of response to the two dosages of nucleoside analog in this group of patients. Measurement of responses will include improvement in the peripheral blood count, reduction in the blood and platelet transfusion need and eradication of cytogenetically abnormal clones. Successful completion of this study will define the position of clofarabine in MDS in the era of epigenetic targeting.

Detailed Description

Study Overview

This study will recruit patients who have received at least six cycles of 5-azacytidine without response or whose disease has progressed or relapsed while on 5-azacytidine. The first cohort of patients will receive clofarabine 10 mg/m2/day for five days and the second cohort of patients 15 mg/m2/day for five days, both every four to six weeks. We will determine the frequency of response to the two dosages of nucleoside analog in this group of patients. Measurement of responses will include improvement in the peripheral blood count, reduction in the blood and platelet transfusion need and eradication of cytogenetically abnormal clones.

  • Primary Objectives

    1. To determine the frequency and duration of peripheral blood responses to IV clofarabine in MDS patients who have failed 5-azacytidine
    2. To determine the frequency and duration of bone marrow responses to IV clofarabine, including CR + PR
  • Secondary Objectives

To determine whether clofarabine exhibits a DNA hypomethylating property

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary Outcome Measure  Improvement in peripheral blood count and reduction in number of transfusions [ Time Frame: after @ least 2 cycles ] [ Designated as safety issue: Yes ]
Secondary Outcome Measure  Eradication in cytogenetically abnormal clones [ Time Frame: after @ least 2 cycles ] [ Designated as safety issue: Yes ]
Condition  Myelodysplastic Syndromes
Intervention  Drug: Clofarabine
MEDLINE PMIDs 16304375,   11222401,   15381930,   12791647,   9696594,   1348362,   10499616,   1707752,   11071652,   12637486,   15486072,   16403905,   16622268,   14551141,   16609072,   17611569
Links Related Info This link exits the ClinicalTrials.gov site
Related Info This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Recruiting
Enrollment  20
Start Date  March 2008
Completion Date March 2011
Eligibility Criteria 

Inclusion Criteria:

  • Patients with MDS of any risk group who have, just immediately prior to being entered into this study, already received at least six cycles of 5-azacytidine and have failed, either due to no response or to disease relapse despite being still on 5-azacytidine, or patients whose MDS has progressed while on 5-azacytidine, irrespective of the number of cycles the patient has received. We have specifically chosen to be very stringent about our patient population in order to address our question of whether clofarabine can be used to salvage patients who have failed 5-azacytidine with only a small patient population, i.e. 10 patients in each cohort.
  • ECOG Performance status of 0 - 2
  • Recombinant erythropoietin is allowed, if the patients are already receiving erythropoietin. G-CSF can be given during the neutropenic stage following therapy since this would not affect evaluation of response because the response will be made based on CBC and bone marrow changes upon recovery from clofarabine.
  • Patients must have been at least four weeks after the last course of 5-azacytidine
  • Age over 18 years
  • Have adequate renal and hepatic functions as indicated by the following laboratory values:

    • Serum creatinine 1.0 mg/dL; if serum creatinine 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
    • Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN)
    • Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 × ULN
    • Alkaline phosphatase 2.5 × ULN
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide signed 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:

  • Nursing or pregnant women
  • Prior clofarabine therapy
  • Life expectancy of less than 3 months due to other intercurrent illness.
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Use of investigational agents within 30 days or any anticancer therapy within 4 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
  • 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.
  • 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).
  • 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.
Gender Both
Ages 18 Years and older
Accepts Healthy Volunteers No
Contacts ††
Contact: Seah Lim, MD     806-358-8654     seah.lim@usoncology.com    
Contact: John McMahan, RN     806-358-8654     john.mcmahan@usoncology.com    
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00700011
Organization ID iCLO111
Secondary IDs ††
Study Sponsor  Texas Oncology Cancer Center
Collaborators †† Genzyme
Investigators 
Principal Investigator:     Seah Lim, MD     Texas Oncology Cancer Center    
Information Provided By Texas Oncology Cancer Center
Verification Date June 2008
First Received Date  June 17, 2008
Last Updated Date June 17, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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