Clofarabine Combinations in Relapsed/Refractory AML, MDS and Myeloid Blast Phase CML - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Genzyme
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00067028

Purpose

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 AML, high-grade MDS, or myeloid blast phase of CML who have relapsed following their initial therapy. In the current extension part of the study, you will only receive the clofarabine/idarubicin/ara-C combination. The activity and the safety of this treatment will be studied.

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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Historical Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Prospective Randomized Phase I/II Study of Clofarabine (Clo) and Ara-C vs Clo and Ida vs Clo Plus Ida and Ara-C in Patients With First Relapse or First Salvage of Primary Refractory AML; and High-Grade MDS(>/= 10% Blasts); or CML in Myeloid Blasts Phase as Front Line Therapy or in First Salvage.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine hydrochloride Idarubicin hydrochloride Idarubicin Clofarabine Cytarabine

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of clofarabine plus idarubicin, and clofarabine plus idarubicin and ara-C. [ Time Frame: July 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete response rate (CR and CRp) of clofarabine plus idarubicin and ara-C vs clofarabine and ara-C vs clofarabine and idarubicin. [ Time Frame: July 2010 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	134
Study Start Date:	December 2003
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Clofarabine + Ara-C: Experimental	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Drug: Ara-C 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
Clofarabine + Idarubicin: Experimental	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Drug: Idarubicin Clofarabine + Idarubicin: 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle. Clofarabine + Idarubicin plus Ara-C: 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Clofarabine + Idarubicin + Ara-C: Experimental	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Drug: Idarubicin Clofarabine + Idarubicin: 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle. Clofarabine + Idarubicin plus Ara-C: 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle. Drug: Ara-C 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age >/= 18 years and < 60 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% 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 </= 2mg/dL, SGPT </= 4 ULN, creatinine </= 2.0mg/dL.
ECOG performance status </= 2.
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 Criteria:

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 of >/= 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.
Cardiac ejection fraction </= 30%.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00067028

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

Genzyme

Investigators

Principal Investigator:

Stefan H Faderl, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The University of Texas M. D. Anderson Cancer Center ( Stefan Faderl M.D./Associate Professor )
Study ID Numbers:	ID03-0181
Study First Received:	August 8, 2003
Last Updated:	October 29, 2009
ClinicalTrials.gov Identifier:	NCT00067028 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Chronic Myeloid Leukemia
CML Myeloid Blast Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Clofarabine
Clofarex
Clolar

Ara-C
Cytarabine
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Idarubicin
Idamycin

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Blast Crisis
Antimetabolites, Antineoplastic
Immunologic Factors
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Leukemia
Neoplastic Processes
Preleukemia
Pathologic Processes

Therapeutic Uses
Syndrome
Cytarabine
Clofarabine
Neoplasms by Histologic Type
Disease
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Leukemia, Myeloid
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Idarubicin

ClinicalTrials.gov processed this record on November 09, 2009