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

NCT00778375 | Completed Phase 2 Results DMC

• 2 other identifiers: 2007-0039NCI-2012-01622
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Keywords

Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome; AML; MDS; Clofarabine; Ara-C; Cytarabine; Decitabine

Outcome Measures

Primary Outcomes (4)

• Disease-free (DFS) or Relapse-free Survival (RFS) Time

  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.

  Evaluated from treatment date until date of disease progression/relapse, followed for 5 years/60 months.

• Complete Remission (CR) Rate for First 60 Participants

  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.

  Evaluation following two 10 day cycles on day 21 of therapy, continuing up to 210 days

• Median Overall Survival (OS)

  Overall survival (OS): Time from date of treatment start until date of death due to any cause.

  Evaluated from treatment date until date of death, followed for 5 years/60 months.

• Number of Participants With Complete Remission [Complete Response (CR), Complete Response With Platelet Recover (CRp) or Complete Response With Incomplete Marrow Recovery (CRi)]

  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.

  Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days

Secondary Outcomes (2)

• Event Free Survival (EFS)

  Follow up up to 5 years/60 months.

• Overall Response Rate (CR, CRp/CRi and PR)

  Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days

Study Arms (1)

Clofarabine + Cytarabine + Decitabine

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Decitabine

Interventions

Clofarabine DRUG

20 mg/m\^2 by vein as a 1- to 2-hour intravenous infusion daily for 5 days.

Also known as: Clolar®, Clorarex

Clofarabine + Cytarabine + Decitabine

Cytarabine DRUG

20 mg subcutaneously twice daily for 10 days, administered 3 to 6 hours following the start of the clofarabine infusions.

Also known as: Cytosar-U®, Ara-C, Arabinosylcytosine

Clofarabine + Cytarabine + Decitabine

Decitabine DRUG

20 mg/m\^2 as a 1- to 2-hour infusion daily for 5 days.

Also known as: Dacogen®

Clofarabine + Cytarabine + Decitabine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \>/= 60 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2.
• 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).
• Sign written informed consent

You may not qualify if:

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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Eisai Inc.: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia

Interventions

Clofarabine; Cytarabine; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Azacitidine; Aza Compounds; Organic Chemicals; Ribonucleosides

Results Point of Contact

• Title: Farhad Ravandi-Kashani, Professor, Leukemia Department
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Farhad Ravandi-Kashani, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 23, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 14, 2016
• Results First Posted: February 26, 2016

Record last verified: 2016-06

Locations

US (1)