Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01289457
First received: February 2, 2011
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control AML and MDS. The safety of these study drug combinations will also be studied.


Condition Intervention Phase
Leukemia
Drug: Clofarabine
Drug: Idarubicin
Drug: Cytarabine
Drug: Fludarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Study of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    MTD is highest dose level in which <2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.


Secondary Outcome Measures:
  • Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) versus Fludarabine, Idarubicin, and Cytarabine (FLAI) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    NCI & MDS International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, Bone marrow aspirate </=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets <100 ×10^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to >10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.

  • Event-Free Survival (EFS) at 2 years [ Time Frame: Up to 2 years or until relapse/death ] [ Designated as safety issue: No ]
    Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.


Estimated Enrollment: 292
Study Start Date: February 2011
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine + Idarubicin + Cytarabine
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
Drug: Clofarabine

Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle.

Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.

Other Names:
  • Clofarex
  • Clolar
Drug: Idarubicin
10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.
Other Name: Idamycin
Drug: Cytarabine
1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinsine Hydrochloride
Experimental: Group 1 CIA
Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Drug: Clofarabine

Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle.

Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.

Other Names:
  • Clofarex
  • Clolar
Drug: Idarubicin
10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.
Other Name: Idamycin
Drug: Cytarabine
1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinsine Hydrochloride
Experimental: Group 2 FLAI
Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Drug: Idarubicin
10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.
Other Name: Idamycin
Drug: Cytarabine
1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinsine Hydrochloride
Drug: Fludarabine
30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Other Name: Fludara

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Sign an IRB-approved informed consent document.
  2. Age 18 to 60. Patients above the age of 60 only with principal investigator (PI) approval
  3. Diagnosis of newly diagnosed AML [other than acute promyelocytic leukemia (APL)] or high-risk (intermediate-2 or high by IPSS or > 10% blasts, including CMML) MDS. Prior therapy with hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m2) for emergency use up to 24 hours prior to start of study therapy is allowed. Prior therapy for MDS or other AHD is not allowed.
  4. ECOG performance status of </= 3 at study entry.
  5. Organ function as defined below (unless due to leukemia): Serum creatinine </= 3 mg/dL Total bilirubin </= 2.5 mg/dL , ALT (SGPT) </= 3 * ULN or </= 5 * ULN if related to disease.
  6. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and must agree to practice acceptable contraceptive methods. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
  7. Cardiac ejection fraction >/= 40% (by either cardiac echo or MUGA scan). Documentation of recent (</= 6 months from screening) outside reports is acceptable.

Exclusion Criteria:

  1. Breast feeding females
  2. Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
  3. Patients with active secondary malignancy will not be eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289457

Contacts
Contact: Elias Jabbour, MD 713-792-4764

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Elias Jabbour, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Elias Jabbour, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01289457     History of Changes
Other Study ID Numbers: 2010-0788, NCI-2011-00251
Study First Received: February 2, 2011
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
AML
High-Risk Myelodysplastic Syndrome
MDS
Relapsed
Refractory
Clofarabine
Clofarex
Clolar
Idarubicin
Idamycin
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid, Acute
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Cytarabine
Fludarabine phosphate
Clofarabine
Fludarabine
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
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 22, 2014