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Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center Identifier:
First received: February 7, 2009
Last updated: August 6, 2013
Last verified: August 2013
This phase I/II trial is studying 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. Drugs used in chemotherapy, such as clofarabine and cytarabine, 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 cytarabine may kill more cancer cells

Condition Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Safety, according to the National Cancer Institute (NCI) Common Terminology Criteria v3.0, as assessed by the MTD of clofarabine when given together with cytarabine [ Time Frame: Occurring 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.

  • Overall response [ Time Frame: Every 3 months for 2 years and then annually for 3 years ]
  • Duration of response [ Time Frame: Every 3 months for 2 years and then annually for 3 years ]
  • Time to treatment failure [ Time Frame: Every 3 months for 2 years and then annually for 3 years ]
  • Overall survival [ Time Frame: Up to 5 years ]

Enrollment: 35
Study Start Date: November 2008
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
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
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Please refer to this study by its identifier: 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/University of Washington Cancer Consortium
National Cancer Institute (NCI)
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Pagel, John, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Identifier: NCT00839982     History of Changes
Other Study ID Numbers: 2302.00
NCI-2010-00039 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA015704 ( US NIH Grant/Contract Award Number )
Study First Received: February 7, 2009
Last Updated: August 6, 2013

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 processed this record on April 28, 2017