Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00814164
Recruitment Status : Terminated (Sponsor withdrew support)
First Posted : December 24, 2008
Results First Posted : August 17, 2016
Last Update Posted : August 17, 2016
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as clofarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving clofarabine together with daunorubicin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving clofarabine together with daunorubicin works in treating older patients with newly diagnosed acute myeloid leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Drug: clofarabine Drug: daunorubicin hydrochloride Genetic: cytogenetic analysis Genetic: protein expression analysis Other: immunologic technique Other: pharmacological study Phase 2

Detailed Description:



  • Study complete response (CR) and CR without platelet recovery (CRp) following treatment with clofarabine and daunorubicin hydrochloride in older patients with newly diagnosed acute myeloid leukemia.


  • Study disease-free and overall survival of these patients following treatment with this regimen.
  • Compare disease-free and overall survival of patients whose cells do or do not demonstrate apoptosis following treatment with this regimen.


  • Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5. Patients are assessed after induction course 1. Patients with ≥ 5% blasts in bone marrow may receive another course of induction therapy beginning between 28-84 days after initiation of course 1. Patients who achieve complete remission (CR) or CR without platelet recovery (CRp) (after 1 or 2 courses of induction therapy) proceed to consolidation therapy.
  • Consolidation therapy: Beginning between 28 -84 days after initiation of last course of induction therapy, patients receive clofarabine IV over 1 hour on days 1-3 and daunorubicin hydrochloride IV over 5 minutes on days 1 and 3. Patients may receive a second course of consolidation therapy beginning between 28-84 days of consolidation course 1.

Blood and bone marrow samples are collected periodically to assess response and for pharmacokinetic, cytogenetic, immunophenotyping, and molecular analyses.

After completion of study treatment, patients are followed for at least 2 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Evaluating Mechanisms of Resistance Following Treatment With Clofarabine and Daunorubicin in Newly Diagnosed Adult Acute Myeloid Leukemia Patients > or = to 60 Years Old
Study Start Date : December 2008
Actual Primary Completion Date : June 2013
Actual Study Completion Date : August 2013

Arm Intervention/treatment
Experimental: Clorafarbine with daunorubicin
Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5.
Drug: clofarabine
Drug: daunorubicin hydrochloride
Genetic: cytogenetic analysis
Correlative study
Genetic: protein expression analysis
Correlative Study
Other: immunologic technique
Correlative Study
Other: pharmacological study
Correlative Study

Primary Outcome Measures :
  1. Complete Remission (CR) [ Time Frame: 2 years ]
    Complete Response/Remission (CR) was defined on morphologic criteria at a single response assessment as follows: A bone marrow aspirate or biopsy of < 5% blasts, with evidence of normal hematopoiesis; Absence of Auer rods in the blast that are present; Absence of extramedullary disease [imaging required only if obtained pretreatment for known site(s) of disease]; If applicable and available, absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; Recovery of peripheral counts (platelets ≥100x109/L, and ANC ≥1.0x109/L). Peripheral count recovery must be documented no earlier than 7 days prior to, and no later than 14 days following, the bone marrow assessment that provides evidence of the CR. Complete Response/Remission without platelet recovery (CRp) was defined as all criteria for CR except for thrombocytopenia (platelet count ≥75x109/L).

Secondary Outcome Measures :
  1. Disease-free Survival [ Time Frame: 5 years ]
    Disease-free survival was defined as time from first objective documentation of CR or CRp until the date of first objective documentation of disease relapse or death due to any cause, whichever occurs first.

  2. Overall Survival [ Time Frame: 4 years ]
    Overall survival was defined as time from date of treatment initiation until date of death due to any cause.

  3. Differences in Disease-free and Overall Survival Between Patients Whose Cells do or do Not Demonstrate Apoptosis Following Clofarabine and Daunorubicin Hydrochloride Therapy [ Time Frame: 4 years ]
  4. Difference in Disease-free and Overall Survival According to p53R2 Protein Sizes [ Time Frame: 4 years ]
  5. Difference in Disease-free and Overall Survival According to Multi-drug Resistance Protein Expression [ Time Frame: 4 years ]
  6. Difference in Disease-free and Overall Survival Based on Clofarabine Triphosphate Levels [ Time Frame: 4 years ]
  7. A Preliminary Relationship Between Treatment Outcome and Biologic Parameters [ Time Frame: 4 years ]

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Ages Eligible for Study:   60 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Newly diagnosed acute myeloid leukemia

    • At least 10% blasts in the peripheral blood
  • De novo or secondary disease
  • No acute promyelocytic leukemia with t[15;17] or any other variant
  • No clinical evidence of CNS disease


  • ECOG performance status 0-2
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • LVEF ≥ 45%
  • Estimated glomerular filtration rate ≥ 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception during and for at least 6 months following study treatment
  • No known HIV positivity
  • Able to comply with study procedures and follow-up examinations
  • No psychiatric disorders that would interfere with consent, study participation, or follow-up
  • No uncontrolled systemic fungal, bacterial, viral, or other infection (i.e., exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)
  • No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo induction therapy with both agents
  • No other malignancy, unless disease-free for at least 3 years following curative intent therapy

    • Nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are allowed if definitive treatment for the condition has been completed
    • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
  • No other severe concurrent disease


  • No other concurrent systemic antileukemic therapy (standard or investigational)
  • No concurrent cytotoxic therapy or investigational therapy
  • No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes)
  • No prior chemotherapy

    • Prior hydroxyurea allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00814164

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Genzyme, a Sanofi Company
Principal Investigator: Meir Wetzler, MD Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute Identifier: NCT00814164     History of Changes
Other Study ID Numbers: CDR0000630678
RPCI-I-132208 ( Other Identifier: Roswell Park Cancer Institute )
First Posted: December 24, 2008    Key Record Dates
Results First Posted: August 17, 2016
Last Update Posted: August 17, 2016
Last Verified: July 2016

Keywords provided by Roswell Park Cancer Institute:
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
untreated adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors