Gleevec/Low-Dose Ara-C Study for Elderly Patients With AML and Myelodysplastic Syndromes

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: NCT00451997
Recruitment Status : Completed
First Posted : March 26, 2007
Last Update Posted : August 1, 2012
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if the combination of Gleevec (imatinib mesylate) and low doses of Cytarabine (ara-C) may help to control leukemia while causing fewer side effects than standard high dose chemotherapy.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid Myelodysplastic Syndromes Drug: Gleevec Drug: Ara-C Phase 2

Detailed Description:

Imatinib mesylate is a drug that blocks a certain protein. This protein is thought to be important in the growth of leukemia cells. Ara-C is a chemotherapy drug that has been used for many years to treat AML and MDS.

Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, as well as the receptor tyrosine kinases for platelet- derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. c-Kit is expressed in over 90% of patients with AML.

The treatment of AML for patients age 65 or older with AML or high-risk MDS (age ³ 60 if high-risk cytogenetics) have a poor prognosis with induction chemotherapy. Response rate is no more than 45% with an induction mortality of at least 25%, and 1-year survival no better than 20%. Indeed, most patients in these age groups are not even offered therapy and are managed with supportive care only. Thus, new therapies that are better tolerated are needed.

Imatinib alone can induce response in nearly 20% of patients, and there is synergy with low concentrations of ara-C. In this study we plan to investigate the combination of imatinib and low-dose ara-C.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Gleevec and Low-Dose Ara-C for Elderly Patients With C-Kit Positive Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes
Study Start Date : March 2004
Actual Primary Completion Date : August 2005
Actual Study Completion Date : April 2007

Arm Intervention/treatment
Experimental: Gleevec + Low-Dose Ara-C Drug: Gleevec
600 mg (capsules) by mouth once daily
Other Names:
  • Imatinib Mesylate
  • STI-571
  • Imatinib
  • NSC-716051
Drug: Ara-C
10 mg as an injection under the skin daily for 21 days of every 28 day cycle
Other Names:
  • Cytarabine
  • Cytosar-U®
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Arabinosylcytosine

Primary Outcome Measures :
  1. Efficacy of a combination of imatinib and low dose ara-C in elderly or high-risk patients with AML and MDS, as measured by the rate of early mortality or progression. [ Time Frame: April 2007 ]

Secondary Outcome Measures :
  1. Rate of overall response, including CRp and PR. [ Time Frame: April 2007 ]
  2. To determine the safety profile of this combination. [ Time Frame: April 2007 ]
  3. To determine the impact on long-term survival of this therapy. [ Time Frame: April 2007 ]
  4. To determine the duration of responses obtained with this therapy. [ Time Frame: April 2007 ]
  5. To determine the impact of this therapy in cognitive function. [ Time Frame: April 2007 ]
  6. To determine the effect of this approach in quality of life of this patient population. [ Time Frame: April 2007 ]
  7. To determine the overall costs (health economic analysis) associated with this combination therapy. [ Time Frame: April 2007 ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Patients who are not candidates for intensive chemotherapy with any of the following diagnosis: 1. AML or MDS (with >/=5% blasts) age >/= 65 years old (or age >/= 60 if high-risk cytogenetics), or 2. AML or MDS (RAEB or RAEBT) of any cytogenetic group age 60 or older with minimally treated disease who have relapsed disease or are refractory to therapy and not likely to require cytoreductive therapy within one month, and, or 3. CMML.
  • Patients with WHO performance status of 0 to 2
  • Patients must have recovered from prior cytotoxic chemotherapy; treatment with hydrea is allowed up to 24 hours prior to day 1 of study drug administration
  • Written informed consent obtained according to local guidelines
  • Patients must have a serum creatinine of </= 1.5 x ULN, SGPT </= 3 x ULN and total bilirubin </= 2.0 x ULN.
  • Patients with >/= 20% blasts positive for c-kit (CD117) (except for CMML)
  • Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of childbearing potential must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

Exclusion Criteria:

  • Patients with uncontrolled active infection
  • Patients with NYHA class III or IV
  • Women who are pregnant
  • Women who are breast feeding

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): NCT00451997

United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Jorge E Cortes, MD The University of M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00451997     History of Changes
Other Study ID Numbers: 2003-0935
First Posted: March 26, 2007    Key Record Dates
Last Update Posted: August 1, 2012
Last Verified: July 2012

Keywords provided by M.D. Anderson Cancer Center:
C-Kit Positive Acute Myeloid Leukemia
High-Risk Myelodysplastic Syndromes

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