Myelodysplastic SyndromesPhase 1NCT00493571
Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes
A Phase 1 study testing Gimatecan in people with Myelodysplastic Syndromes and MDS, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, MDS
- What is being tested?
- Gimatecan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to May 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with MDS with >/= 5% blasts or IPSS risk group intermediate (1 or 2) or high (i.e., IPSS score 0.5 or higher).
- 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).
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- 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.
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have received only supportive care (transfusions and/or hematopoietic growth factors) for MDS.
- 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.
- 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.
- Women who are pregnant or breast-feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
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).
Read the detailed description
The Study Drug:
Gimatecan is designed to block the function of an important protein (topoisomerase I) in cancer cells that helps repair damage to DNA (the genetic material of cells). When this protein is blocked, cancer cells may die.
Screening Tests:
Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.
- You will have a physical exam.
- Your complete medical history will be recorded.
- Your vital signs (blood pressure, pulse, breathing rate, and temperature), height, and weight will be measured.
- You will be asked how well you are able to perform the normal activities of daily living (a performance status evaluation).
- You will be asked about any medications you may be taking.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Women who are able to have children must have a negative blood (about 2 teaspoons) or urine pregnancy test.
- You will have a bone marrow aspirate performed. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
- If your doctor thinks it is necessary, you will have a bone marrow biopsy when you have the bone marrow aspirate done. To collect a bone marrow biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- You will complete a questionnaire to see how the disease may be affecting your ability to do your daily activities. The questionnaire will take about 15 minutes to complete.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, the amount of study drug you receive will be based on when you join the study. Three (3) to 6 participants will be enrolled in this study and given a certain dose. If they do not experience intolerable side effects, the next 3-6 participants enrolled will receive a higher dose. This process will continue until researchers find the highest dose of the drug that can be given without causing serious or intolerable side effects. The study doctor will tell you what dose you will be receiving and how this compares to the doses other participants have received.
Study Drug Administration:
You will take gimatecan on Days 1-5. On Days 6-28, you will take no study drug. Each 28-day period is called a study "cycle." If your doctor thinks it is necessary, your study cycles may be shortened so that you will receive the study drug more often.
You will take the medication on an empty stomach, swallowing the capsules whole. You should not eat for 1 hour after taking the medication. If you take other medications while you are on this study, they must be taken 4 hours before or after you take gimatecan.
Study Visits:
Blood (about 2 tablespoons each time) will be drawn for routine tests every 1-4 weeks for the length of this study. Most of these blood tests will be done once a week, but some will only be done once every 4 weeks.
You will have a physical exam every 4 weeks for the first 3 months, then every 3 months.
At the end of Cycle 1, and then every 9-12 weeks after that, you will have a bone marrow aspirate and/or biopsy. Bone marrow biopsies and aspirates may be collected more often if your study doctor thinks it is necessary.
Once per week for the first 3 cycles, you will complete a symptom questionnaire. This will be done either at a study visit, or you will be called by a member of study staff. The questionnaire will take about 15 minutes to complete.
Length of Study:
You can remain on this study for up to 12 months. If, after this time, it is considered that gimatecan is helping you, the study doctor will discuss the possibility of continuing the study drug therapy outside of this study. You may be taken off this study early if the disease gets worse or intolerable side effects occur.
End-of-Study Visit:
Once you are off this study, you will have an end-of-study visit, and the following tests will be performed.
- You will have a physical exam.
- You will be asked about any side effects you may be experiencing.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- You will repeat the symptom questionnaire.
This is an investigational study. Gimatecan is not FDA approved or commercially available. It has been authorized for use in research only. Up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Myelodysplastic Syndromes, MDS
- Being tested
- Gimatecan
- Keywords
- Myelodysplastic Syndromes, MDS, Gimatecan, Leukemia
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GimatecanDrug
Starting dose: 0.6 mg capsules administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Gimatecan | Experimental | Gimatecan Starting dose: 0.6 mg capsules administered orally once daily. Receives: Drug: Gimatecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Gimatecan
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.
Measured: Evaulate with each 28 Day Cycle
Secondary outcomes (1)
Efficacy in terms of complete remission , complete remission w/ incomplete platelet or neutrophil recovery (CRp and CRn, respectively), partial remission , and hematologic improvement.
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.
Measured: Up to 12 Months on Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2007 (estimated)
- Study startAug 2007
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Jorge E. Cortes, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00493571
- Sponsor's protocol ID
- 2006-0943
- Other IDs
- NCI-2010-00622
- Status last verified
- May 2015
- First submitted
- 27 Jun 2007
- Last updated
- 13 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00493571
- Acronym / sponsor ID
- 2006-0943
- Conditions
- Myelodysplastic Syndromes, MDS
- Keywords
- Myelodysplastic Syndromes, MDS, Gimatecan, Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2007
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The Study Drug:
Gimatecan is designed to block the function of an important protein (topoisomerase I) in cancer cells that helps repair damage to DNA (the genetic material of cells). When this protein is blocked, cancer cells may die.
Screening Tests:
Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.
- You will have a physical exam.
- Your complete medical history will be recorded.
- Your vital signs (blood pressure, pulse, breathing rate, and temperature), height, and weight will be measured.
- You will be asked how well you are able to perform the normal activities of daily living (a performance status evaluation).
- You will be asked about any medications you may be taking.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Women who are able to have children must have a negative blood (about 2 teaspoons) or urine pregnancy test.
- You will have a bone marrow aspirate performed. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
- If your doctor thinks it is necessary, you will have a bone marrow biopsy when you have the bone marrow aspirate done. To collect a bone marrow biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- You will complete a questionnaire to see how the disease may be affecting your ability to do your daily activities. The questionnaire will take about 15 minutes to complete.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, the amount of study drug you receive will be based on when you join the study. Three (3) to 6 participants will be enrolled in this study and given a certain dose. If they do not experience intolerable side effects, the next 3-6 participants enrolled will receive a higher dose. This process will continue until researchers find the highest dose of the drug that can be given without causing serious or intolerable side effects. The study doctor will tell you what dose you will be receiving and how this compares to the doses other participants have received.
Study Drug Administration:
You will take gimatecan on Days 1-5. On Days 6-28, you will take no study drug. Each 28-day period is called a study "cycle." If your doctor thinks it is necessary, your study cycles may be shortened so that you will receive the study drug more often.
You will take the medication on an empty stomach, swallowing the capsules whole. You should not eat for 1 hour after taking the medication. If you take other medications while you are on this study, they must be taken 4 hours before or after you take gimatecan.
Study Visits:
Blood (about 2 tablespoons each time) will be drawn for routine tests every 1-4 weeks for the length of this study. Most of these blood tests will be done once a week, but some will only be done once every 4 weeks.
You will have a physical exam every 4 weeks for the first 3 months, then every 3 months.
At the end of Cycle 1, and then every 9-12 weeks after that, you will have a bone marrow aspirate and/or biopsy. Bone marrow biopsies and aspirates may be collected more often if your study doctor thinks it is necessary.
Once per week for the first 3 cycles, you will complete a symptom questionnaire. This will be done either at a study visit, or you will be called by a member of study staff. The questionnaire will take about 15 minutes to complete.
Length of Study:
You can remain on this study for up to 12 months. If, after this time, it is considered that gimatecan is helping you, the study doctor will discuss the possibility of continuing the study drug therapy outside of this study. You may be taken off this study early if the disease gets worse or intolerable side effects occur.
End-of-Study Visit:
Once you are off this study, you will have an end-of-study visit, and the following tests will be performed.
- You will have a physical exam.
- You will be asked about any side effects you may be experiencing.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- You will repeat the symptom questionnaire.
This is an investigational study. Gimatecan is not FDA approved or commercially available. It has been authorized for use in research only. Up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gimatecan | Experimental | Drug: GimatecanGimatecan Starting dose: 0.6 mg capsules administered orally once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with MDS with >/= 5% blasts or IPSS risk group intermediate (1 or 2) or high (i.e., IPSS score 0.5 or higher).
- 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).
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- 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.
Key exclusion criteria (4 listed)
- Patients who have received only supportive care (transfusions and/or hematopoietic growth factors) for MDS.
- 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.
- 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.
- Women who are pregnant or breast-feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GimatecanStarting dose: 0.6 mg capsules administered orally once daily. | Drug | Gimatecan |
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2015.
- M.D. Anderson's websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge E. Cortes, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gimatecan in people with Myelodysplastic Syndromes and MDS, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Gimatecan (time frame: Evaulate with each 28 Day Cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2015.