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 (Responsible Party):	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 Acute Myeloid Leukemia, high-grade MDS, or myeloid blast phase of Chronic Myeloid Leukemia 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:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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: Acute Myeloid Leukemia Cancer Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

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: 21 days ] [ Designated as safety issue: No ]
Bone marrow aspirate starting on day 21 (+/- 7 days) of therapy and every 2 weeks thereafter (+/- 7 days) until remission or non-response.

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:	120
Study Start Date:	December 2003
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Clofarabine + Ara-C	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Other Names: Clofarex Clolar Drug: Ara-C Starting dose: 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle. Other Names: Cytosar-U® Cytarabine Cytosar DepoCyt Cytosine arabinosine hydrochloride
Experimental: Clofarabine + Idarubicin	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Other Names: Clofarex Clolar 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. Other Names: Idamycin®, Idamycin PFS®
Experimental: Clofarabine + Idarubicin + Ara-C	Drug: Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days. Other Names: Clofarex Clolar 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. Other Names: Idamycin®, Idamycin PFS® Drug: Ara-C Starting dose: 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle. Other Names: Cytosar-U® Cytarabine Cytosar DepoCyt Cytosine arabinosine hydrochloride

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 59 Years
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
UT MD 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:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00067028 History of Changes
Other Study ID Numbers:	ID03-0181
Study First Received:	August 8, 2003
Last Updated:	October 19, 2011
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:

Blast Crisis
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes

Precancerous Conditions
Cytarabine
Clofarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012