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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00451997
First received: March 23, 2007
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Leukemia, Myeloid
Myelodysplastic Syndromes
Drug: Gleevec
Drug: Ara-C
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of overall response, including CRp and PR. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]
  • To determine the safety profile of this combination. [ Time Frame: April 2007 ] [ Designated as safety issue: Yes ]
  • To determine the impact on long-term survival of this therapy. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]
  • To determine the duration of responses obtained with this therapy. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]
  • To determine the impact of this therapy in cognitive function. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]
  • To determine the effect of this approach in quality of life of this patient population. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]
  • To determine the overall costs (health economic analysis) associated with this combination therapy. [ Time Frame: April 2007 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: March 2004
Study Completion Date: April 2007
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451997

Locations
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
Novartis
Investigators
Principal Investigator: Jorge E Cortes, MD The University of M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00451997     History of Changes
Other Study ID Numbers: 2003-0935
Study First Received: March 23, 2007
Last Updated: July 31, 2012
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on July 24, 2014