Phase I Study of Gimatecan in Patients With 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: NCT00493571
Recruitment Status : Completed
First Posted : June 28, 2007
Last Update Posted : May 13, 2015
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to find the highest tolerable dose of gimatecan that can be given to treat myelodysplastic syndrome (MDS).

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes MDS Drug: Gimatecan Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes
Study Start Date : August 2007
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gimatecan
Gimatecan Starting dose: 0.6 mg capsules administered orally once daily.
Drug: Gimatecan
Starting dose: 0.6 mg capsules administered orally once daily.

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Gimatecan [ Time Frame: Evaulate with each 28 Day Cycle ]
    For purposes of estimating the MTD, 5 dose levels of Gimatecan initially considered. These dose levels are 3 mg, 5 mg, 7.5 mg, 8.75 mg, and 10 mg orally per cycle. Dose escalation based on toxicities observed through the first cycle.

Secondary Outcome Measures :
  1. Efficacy in terms of complete remission , complete remission w/ incomplete platelet or neutrophil recovery (CRp and CRn, respectively), partial remission , and hematologic improvement. [ Time Frame: Up to 12 Months on Study ]
    Response criteria according to the International Working Group (Blood 2006; 108: 419-425). Responders are patients who obtain a Complete Response (CR), CRi, Partial Response (PR), with or without cytogenetic response, hematologic improvements, and morphologic leukemia-free state.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with MDS with >/= 5% blasts or IPSS risk group intermediate (1 or 2) or high (i.e., IPSS score 0.5 or higher).
  2. Patients must have failed prior therapy with either chemotherapy (e.g., ara-C-based chemotherapy, etc) or biologic agents (e.g., hypomethylating agents, arsenic, thalidomide, CC5013, farnesyl transferase inhibitors, ATG, cyclosporine, etc).
  3. Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of Gimatecan in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  5. Patients must have normal organ function as defined below: 1) Total bilirubin: </= 1.5 x institutional upper limit of normal; 2) ALT(SGPT): </= 2.5 x institutional upper limit of normal; 3) Creatinine: </= 1.5 x institutional upper limit of normal.
  6. The effects of Gimatecan on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential (ie, not post-menopausal for at least 12 months and not surgically sterile) and men must agree to use double-barrier contraception prior to study entry, for the duration of study participation, and for 3 months following discontinuation of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients who have received only supportive care (transfusions and/or hematopoietic growth factors) for MDS.
  2. Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives of the agent in question (6 weeks for nitrosoureas or mitomycin C), whichever is greater, prior to entering the study or those who have not recovered to at least grade 1 from adverse events due to agents administered more than 4 weeks earlier. The use of hydroxyurea is allowed up to 48 hours prior to the start of therapy with Gimatecan.
  3. Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia requiring and not responding to medical intervention, or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Women who are pregnant or 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): NCT00493571

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 M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00493571     History of Changes
Other Study ID Numbers: 2006-0943
NCI-2010-00622 ( Registry Identifier: NCI CTRP )
First Posted: June 28, 2007    Key Record Dates
Last Update Posted: May 13, 2015
Last Verified: May 2015

Keywords provided by M.D. Anderson Cancer Center:
Myelodysplastic Syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action