Clofarabine and Cytarabine in Treating Older Patients With AML or High-Risk MDS

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: NCT00839982
Recruitment Status : Completed
First Posted : February 10, 2009
Results First Posted : July 11, 2017
Last Update Posted : July 11, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
This phase I/II trial studied the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) that have relapsed or not responded to treatment.

Condition or disease Intervention/treatment Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) 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) Myelodysplastic Syndrome With Isolated Del(5q) Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Myeloid Leukemia Drug: clofarabine Drug: cytarabine Phase 1 Phase 2

Detailed Description:


I. To estimate the maximum tolerated dose (MTD) of oral clofarabine when given with LDAC (cytarabine) in patients age >= 60 with previously treated AML or high risk MDS.


I. To determine the response rate, disease-free survival (DFS), and overall survival (OS) after therapy with oral clofarabine and LDAC for previously treated AML or high-risk MDS.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study.

Patients receive clofarabine orally (PO) once daily (QD) on days 1-5 and low-dose cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of Oral Clofarabine Plus Low-dose Cytarabine in Previously Treated AML and High-Risk MDS Patients at Least 60 Years of Age
Study Start Date : November 2008
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: Treatment (chemotherapy)
Patients receive clofarabine PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: clofarabine
Given PO
Other Names:
  • CAFdA
  • Clofarex
  • Clolar

Drug: cytarabine
Given SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

Primary Outcome Measures :
  1. Number of Patients With Dose Limiting Toxicity [ Time Frame: Outcomes by day 30 ]
    Dose limiting toxicity (DLT) consists of grade 3-4 non-hematologic toxicity at least possibly related to study drug. Exceptions include neutropenic fever; drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin recovering to < grade 2 by 7 days. Prolonged grade 2 myelosuppression lasting longer than 49 days in patients who don't proceed to additional cytotoxic therapy is considered a DLT. The MTD or recommended phase II dose is the highest dose level at which no more than 1 patient out of 6 experiences DLT.

  2. Maximum Tolerated Dose [ Time Frame: up to 5 years ]
    We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine.

Secondary Outcome Measures :
  1. Treatment Response [ Time Frame: Up to 5 years ]
    CR = no evidence of leukemia with complete blood count recovery (ANC >1,000 and PLTS >100k) CRi = no evidence of leukemia but with incomplete blood count recovery

  2. Disease Free Survival [ Time Frame: Up to 5 years ]
    Median disease-free survival

  3. Overall Survival [ Time Frame: Up to 5 years ]
    Median overall survival

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of 1st relapse or refractory AML; or patients with high risk MDS (10-19% blasts) who have received previous therapy 1st remission must have been < 1 year
  • Must not have received previous ara-C (cytarabine) or clofarabine
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Not candidates for standard 7 + 3 regimen (Ara-C and an anthracycline), high dose Ara-C, or hematopoietic stem-cell transplantation
  • Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 50 L/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
  • Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
  • Male and female patients should use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Exclusion Criteria:

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
  • Patients with acute promyelocytic leukemia (APL)
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea; the patient must have recovered from all acute toxicities from any previous therapy
  • Have any other severe concurrent disease, or have a 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 treatment
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
  • Pregnant or lactating patients
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  • Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy including the following:

    • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study 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 (PSA) values are also eligible for this study if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed
  • Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine

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): NCT00839982

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Responsible Party: Fred Hutchinson Cancer Research Center Identifier: NCT00839982     History of Changes
Other Study ID Numbers: 2302.00
NCI-2010-00039 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: February 10, 2009    Key Record Dates
Results First Posted: July 11, 2017
Last Update Posted: July 11, 2017
Last Verified: July 2017

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