Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00493571
First received: June 27, 2007
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Myelodysplastic Syndromes
MDS
Drug: Gimatecan
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Gimatecan [ Time Frame: Evaulate with each 28 Day Cycle ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 16
Study Start Date: August 2007
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00493571

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 M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00493571     History of Changes
Other Study ID Numbers: 2006-0943, NCI-2010-00622
Study First Received: June 27, 2007
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on October 23, 2014