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A Dose Confirmation Study of Oral Clofarabine for Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS)

Information source: Sanofi
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myelodysplastic Syndromes; Secondary AML

Intervention: clofarabine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Genzyme, a Sanofi Company

Official(s) and/or principal investigator(s):
Medical Monitor, Study Director, Affiliation: Genzyme, a Sanofi Company

Summary

There is no well accepted standard care for patients who fail or are intolerant to any of the currently approved therapies for Myelodysplastic Syndromes (MDS). In this study, patients will be assigned to receive 25mg of oral clofarabine daily for 5 days. Patients may receive up to 8 cycles of treatment with clofarabine as long as the patient continues to benefit and in the absence of progressive disease.

Clinical Details

Official title: A Phase IIa Open-label, Dose Confirmation Study of Oral Clofarabine in Adult Patients Previously Treated for Myelodysplastic Syndromes(MDS)

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

Primary outcome: Maximum Tolerated dose of oral clofarabine (dosed daily x 5) for treatment of previously treated adult patients with MDS or secondary acute myeloid leukemia (following a history of MDS).

Secondary outcome:

The rate of febrile neutropenia and the toxicity profile for each dose under study.

Efficacy parameters: hematologic improvement(HI);overall response rate/duration (CR,marrow CR,PR,or HI); overall remission rate (CR,marrow CR,or PR);time to AML transformation; overall survival (OS)

Clofarabine pharmacokinetics (PK) after oral administration

Eligibility

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

Criteria:

Inclusion Criteria:

- Have a pathologically confirmed secondary Acute Myeloid Leukemia (following a history

of MDS) or MDS with an intermediate 1 (with marrow blasts great than or equal to 5%) intermediate 2 or high risk score as assessed by the International Prognostic Scoring System (IPSS) at study, entry. Patients with refractory anemia with excess blasts in transformation (RAEB-t) recognized by the French-American-British (FAB) system, and chronic myelomonocytic leukemia (CMML) will be allowed into the study. Pathologic confirmation is the responsibility of the site investigator.

- Have previously treated MDS defined as follows: a.)Patients must have had at least

one, but no more than two, prior treatment regimens [A treatment regimen is defined as any drug or drug combination administered for treatment of MDS with the intent of inducing at least hematologic improvement (consistent with International Working Group [IWG] criteria); Inadequate treatment, due to drug intolerance or other factors, will still be considered a prior treatment regimen. Hematopoietic growth factors, hydroxyurea, anti-thymocyte globulin (ATG), or supportive care measures (e. g., blood transfusions, immunosuppressive agents, antibiotics) will not be considered treatment regimens for the purpose of study entry.] b.)One of the treatment regimens must have been either 5-azacytidine or decitabine. If 5-azacytidine or decitabine is given as a treatment regimen more than once, it will be considered as 2 different treatment regimens. c.)Patients must not have been refractory (i. e., progression of disease, or no evidence of response, while on the treatment) to more than one prior treatment regimen (to be considered refractory to decitabine or 5-azacitidine, patients must have received greater than or equal to 4 cycles).

- Have documentation of prior transfusion requirements for the preceding 8 weeks (8

weeks prior to first dose of study drug).

- Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

- Be able to comply with study procedures and follow-up examinations.

- Have adequate renal and hepatic functions as indicated by predefined laboratory

values: a.)Total bilirubin < 1. 5 x institutional Upper Limit of Normal (ULN) except for unconjugated hyperbilirubin secondary to treatment for MDS or Gilbert's syndrome; and b.)Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) < 2. 5 x ULN; and c.)Serum creatine < 1. 0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >30 mL/min/1. 73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation.

- Be non-fertile or agree to use birth control during the study through the end of last

treatment visit and at least 90 days after. Exclusion Criteria:

- Have had an adjustment of dose and/or schedule of erythropoietin, granulocyte colony

stimulating factor (G-CSF) or other growth factors within 8 weeks prior to the first dose of oral clofarabine.

- Have had any prior therapy for treatment of sAML. Hydroxyurea must not have been

received within 24 hours prior to first dose of study drug.

- Have had any other chemotherapy or any investigational therapy within four weeks of

first dose of study drug.

- Have had any prior pelvic radiotherapy.

- Have had a prior hematopoietic stem cell transplant for MDS.

- Have not recovered to < grade 2 from any drug-related non-hematologic toxicity prior

to first dose of the study drug.

- Have an uncontrolled systemic fungal, bacterial, viral, or other infection (defined

as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

- Have a psychiatric disorder that would interfere with consent, study participation,

or follow-up.

- Have any other severe concurrent disease, or have a history of serious organ

dysfunction or disease involving the heart, kidney, or liver, in particular: a.)New York Heart Association (NHA) classification stage II, III, or IV congestive heart failure; b.)Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c.)Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.

- Have any other severe concurrent disease, or have a history of serious organ

dysfunction or disease involving the heart 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: a.)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. b.)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 (HIV).

- Have currently active gastrointestinal disease, or prior surgery that may affect the

ability of the patient to absorb oral clofarabine.

- Participating in other concurrent investigational protocols that are not restricted

to data and/or sample collection for patient demographic and/or sample collection for patient demographic and/or disease purposes.

- Have had prior treatment with a known nephrotoxic drug within 2 weeks of the first

dose of study drug, unless the patient has a calculated GFR >30 at 2 time points no less than 7 days apart during the 2-week period prior to the first dose of study drug.

Locations and Contacts

The University of Chicago, Chicago, Illinois 60637, United States

Weill Medical College of Cornell University, New York, New York 10065, United States

Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

Baylor University Medical Center Blood Marrow Transplantation Research, Dallas, Texas 75246, United States

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States

Additional Information

Starting date: September 2007
Last updated: March 17, 2014

Page last updated: August 23, 2015

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