The goal of this clinical research study is to find the best safe dose for 2 different drug combinations. For this purpose, participants will either receive the combination of clofarabine plus idarubicin or clofarabine plus idarubicin and ara-C. Once the best safe dose for these drug combinations are found, the next goal is to compare the drug combinations clofarabine/idarubicin/ara-C, clofarabine/ara-C, and clofarabine/idarubicin in the treatment of patients with acute myeloid leukemia (AML), high-grade myelodysplastic syndrome (MDS), or myeloid blast phase of chronic myeloid leukemia (CML) who have relapsed following their initial therapy. The safety of these treatments will also be studied.

Condition	Treatment or Intervention	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Chronic Myeloid Leukemia	Drug: clofarabine  Drug: Idarubicin  Drug: Ara-C	Phase II

Further Study Details: 

Primary Outcomes: 1. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of clofarabine plus idarubicin, and clofarabine plus idarubicin and ara-C.; 2. To determine the complete response rate (CR and CRp) of clofarabine plus idarubicin and ara-C vs clofarabine and ara-C vs clofarabine and idarubicin. The primary efficacy endpoint will be success defined as the number of patients achieving CR/CRp.; 3. To compare the toxicity profiles of clofarabine plus idarubicin and ara-C vs clofarabine and ara-C vs clofarabine and idarubicin.; 4. To compare response duration (CR/CRp) and survival of clofarabine plus idarubicin and ara-C vs clofarabine and ara-C vs clofarabine and idarubicin.
Expected Total Enrollment:  90

Therapeutic options for patients with advanced acute leukemias are limited and the prognosis of these patients is dismal. Hence the need to incorporate new and active drugs into the treatment of these patients. Nucleoside analogs are among the most active anti-leukemic agents. Clofarabine is a novel nucleoside analog with unique metabolic and pharmacokinetic characteristics. Clofarabine has shown to be active in phase I and II studies of patients with relapsed and refractory acute leukemias. This protocol will combine clofarabine with the two currently most powerful antileukemic agents and allow us to proceed to more effective combination therapy.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion:

• Age > 18 years.
• Must be in first relapse of AML, or must receive treatment as first salvage in primary refractory AML; or have high-risk MDS (> 10% bone marrow blasts) with not more than one prior regimen of chemotherapy (therapy with hematopoietic growth factors, biological or targeted therapies are not counted). Patients in CML myeloid blast phase may receive clofarabine as frontline therapy or in first salvage.
• Total bilirubin < 2 mg/dL, SGPT < 4 ULN, creatinine < 2mg/dL.
• ECOG performance status < 2.
• Cardiac ejection fraction <= 30% (by MUGA scan or echocardiography)
• Signed informed consent.
• Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized).

Exclusion:

• Previous treatment with clofarabine
• Active, uncontrolled, systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment, or any severe, concurrent disease, which, in the judgment of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for study entry.
• Symptomatic CNS involvement.
• Patients who receive other chemotherapy. Patients must have been off previous therapy for > 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. Treatment may start earlier following discussion with the Principal Investigator.

Stefan H Faderl, MD      713-745-4613    sfaderl@mdanderson.org

Texas
      M.D. Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

Stefan H Faderl, MD,  Principal Investigator,  University of Texas M.D. Anderson Cancer Center   

Study ID Numbers:  ID03-0181
Record last reviewed:  November 2004
Last Updated:  November 1, 2004
Record first received:  August 8, 2003
ClinicalTrials.gov Identifier:  NCT00067028
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08