Clofarabine Combinations in Relapsed/Refractory AML, MDS and Myeloid Blast Phase CML

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00067028
First received: August 8, 2003
Last updated: June 17, 2013
Last verified: June 2013
  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 2

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:


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: Assessed with each dose level, 21 days ] [ Designated as safety issue: No ]
    MTD defined as the dose level at which one patient develops DLT, then the previous dose considered the MTD where Toxicity graded according to NCI Common Toxicity Criteria Version 3.0. No new patients entered at the escalated dose level until at least 2 patients have completed one treatment cycle and the third patient has completed two weeks of the cycle and no evidence of dose-limiting toxicity has been seen.


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: 21 days ] [ Designated as safety issue: No ]
    Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count > 1.0 x109/L and platelet count >100x109/L, and normal bone marrow differential (< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of > 20 x 109/L and < 100 x 109/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of > 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.


Enrollment: 166
Study Start Date: December 2003
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine + Ara-C

Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days.

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.

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

Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days.

Idarubicin 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.

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

Clofarabine 30 - 40 mg/m^2 by vein over 1 hour daily for 5 days.

Idarubicin 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.

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.

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:

  1. Age >/= 18 years and < 60 years.
  2. 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.
  3. Total bilirubin </= 2mg/dL, Serum glutamic pyruvic transaminase (SGPT) </= 4 upper limit of normal (ULN), creatinine </= 2.0mg/dL.
  4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
  5. Signed informed consent.
  6. 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:

  1. Previous treatment with clofarabine.
  2. 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.
  3. Symptomatic central nervous system (CNS) involvement.
  4. 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.
  5. Cardiac ejection fraction </= 30%.
  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: NCT00067028

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Stefan H Faderl, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
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: June 17, 2013
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 July 28, 2014