Clofarabine Plus Low-Dose Cytarabine Induction and Decitabine Consolidation in Frontline Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)

This study has been completed.
Sponsor:
Collaborators:
Eisai Inc.
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00778375
First received: October 21, 2008
Last updated: June 15, 2016
Last verified: June 2016
  Purpose
The goal of this clinical research study is to learn if clofarabine given in combination with cytarabine and decitabine can help to control the disease in patients with AML or MDS who are 60 years old or older. The safety of this treatment will also be studied.

Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: Clofarabine
Drug: Cytarabine
Drug: Decitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clofarabine Plus Low-Dose Cytarabine Induction Followed by Consolidation of Clofarabine Plus Low-Dose Cytarabine Alternating With Decitabine in Frontline Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free (DFS) or Relapse-free Survival (RFS) Time [ Time Frame: Evaluated from treatment date until date of disease progression/relapse, followed for 5 years/60 months. ] [ Designated as safety issue: No ]
    Disease (DFS) or Relapse-free survival (RFS): Time from date of treatment start until the date of first objective documentation of disease-relapse; Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy and then every 2 weeks (+/- 7 days) as required by leukemia evolution until remission or non-response. Among participants who achieved CR or CRp, RFS was defined as the time interval between the date of response (ie CR or CRp) and the date of relapse or date of death, whichever occurs first. CR or CRp participants who were alive and relapse-free were censored at the off-study date. Full range reflects time to disease progression only, therefore does not reflect a lesser survival time due to other reasons than disease progression/relapse.

  • Complete Remission (CR) Rate for First 60 Participants [ Time Frame: Evaluation following two 10 day cycles on day 21 of therapy, continuing up to 210 days ] [ Designated as safety issue: No ]
    All responses were defined as per IWG criteria (2003) where CR Rate defined as number of participants with CR out of total treated participants. Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/L, and normal bone marrow differential (< 5% blasts). Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy.

  • Median Overall Survival (OS) [ Time Frame: Evaluated from treatment date until date of death, followed for 5 years/60 months. ] [ Designated as safety issue: No ]
    Overall survival (OS): Time from date of treatment start until date of death due to any cause.

  • Number of Participants With Complete Remission [Complete Response (CR), Complete Response With Platelet Recover (CRp) or Complete Response With Incomplete Marrow Recovery (CRi)] [ Time Frame: Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days ] [ Designated as safety issue: No ]
    All responses were defined as per IWG criteria (2003) where CR Rate defined as number of participants with CR out of total treated participants. Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/L, and normal bone marrow differential (< 5% blasts). Complete response with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts. Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy.


Secondary Outcome Measures:
  • Event Free Survival (EFS) [ Time Frame: Follow up up to 5 years/60 months. ] [ Designated as safety issue: No ]
    EFS is defined as length of time after primary treatment for a cancer ends that the participant remains free of certain complications or events that the treatment was intended to prevent or delay, for example but not exclusive of hematologic and non-hematologic toxicities, cumulative toxicities with consolidation courses, or emergence of resistance to the chemotherapy component of treatment.

  • Overall Response Rate (CR, CRp/CRi and PR) [ Time Frame: Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days ] [ Designated as safety issue: No ]
    IWG Response criteria (2003): Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/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 < 100 x 10^9/L or Complete remission with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts; Partial Remission (PR): Blood count recovery as for CR, but with both a decrease in marrow blasts of at least 50% and not more than 6 to 25% abnormal cells in the marrow. Participants not achieving a complete remission following first induction course, can receive a second induction course at least 28 days following first to optimize response if possible.


Enrollment: 122
Study Start Date: October 2008
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine + Cytarabine + Decitabine
Clofarabine 20 mg/m^2 by vein (IV) as a 1- to 2-hour intravenous infusion daily for 5 days. Cytarabine 20 mg subcutaneously twice daily for 10 days, administered 3 to 6 hours following the start of the clofarabine infusions. Decitabine 20 mg/m^2 as a 1- to 2-hour infusion daily for 5 days.
Drug: Clofarabine
20 mg/m^2 by vein as a 1- to 2-hour intravenous infusion daily for 5 days.
Other Names:
  • Clolar®
  • Clorarex
Drug: Cytarabine
20 mg subcutaneously twice daily for 10 days, administered 3 to 6 hours following the start of the clofarabine infusions.
Other Names:
  • Cytosar-U®
  • Ara-C
  • Arabinosylcytosine
Drug: Decitabine
20 mg/m^2 as a 1- to 2-hour infusion daily for 5 days.
Other Name: Dacogen®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Previously untreated AML and high-risk MDS (>/= 10% blasts or >/= IPSS intermediate-2). Prior therapy with hydroxyurea, biological or targeted therapy (e.g. flt3 inhibitors, other kinase inhibitors, azacitidine), or hematopoietic growth factors is allowed.
  2. Age >/= 60 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
  4. Adequate hepatic (serum total bilirubin </= 1.5 x ULN, serum glutamate pyruvate transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) </= 2.5 x ULN) and renal function (creatinine </= 1.5 mg/dL).
  5. Sign written informed consent

Exclusion Criteria:

  1. Cardiac ejection fraction < 40%.
  2. Prior therapy with clofarabine or decitabine.
  3. Active and uncontrolled disease/infection as judged by the treating physician.
  4. Pregnancy
  5. Acute promyelocytic leukemia (APL).
  6. Women of childbearing potential and men who do not practice contraception.
  7. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  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: NCT00778375

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Eisai Inc.
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Farhad Ravandi-Kashani, M.D. M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00778375     History of Changes
Other Study ID Numbers: 2007-0039  NCI-2012-01622 
Study First Received: October 21, 2008
Results First Received: January 28, 2016
Last Updated: June 15, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndrome
AML
MDS
Clofarabine
Ara-C
Cytarabine
Decitabine

Additional relevant MeSH terms:
Leukemia
Syndrome
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Clofarabine
Decitabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2016