Myelodysplastic Syndrome (MDS)Phase 1NCT01286038
Eltrombopag in Myelodysplastic Syndrome (MDS) Patients With Thrombocytopenia
A Phase 1 study testing Eltrombopag in people with Myelodysplastic Syndrome (MDS) and Thrombocytopenia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of eltrombopag in people who have myelodysplastic syndrome (MDS) with thrombocytopenia who have progressed or are resistant to decitabine or azacitidine. (These are the only 2 drugs approved by the U.S. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome (MDS), Thrombocytopenia
- What is being tested?
- Eltrombopag
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2011to 3 Nov 2018
- 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
- Confirmed diagnosis of MDS using the World Health Organization (WHO) classification or a diagnosis of WHO Myelodysplastic/ Myeloproliferative Neoplasm (MDS/MPN) or MDS refractory anemia with excess blast in transformation (RAEB-t) by French American British (FAB) classification (AML with 20-30% myeloblasts by WHO classification).
- All prognostic risk groups according to the International Prognostic Scoring System (IPSS) and MD Anderson Risk Model
- At least one prior HMTA treatment with either azacitidine or decitabine and subsequent loss of response to HMTA, progression while on HMTA, or no response to HMTA, defined as failure to achieve at least HI after 4 cycles of treatment
- The mean of the two platelet counts taken within 1 month prior to dosing must be ≤50 x 10^9/L. Platelets counts must reflect pre-transfusion trough results or be obtained no sooner than 1 week after platelet transfusion to assure stable baseline platelet count. The platelet count obtained should be outside the expected nadir of prior therapies.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >60%
- Adequate liver function, as evidenced by total serum bilirubin ≤ 1.5 times the upper limit of normal (patients with Gilbert's disease are eligible, provided intermittent indirect hyperbilirubinemia), aspartic transaminase (AST) or alanine transaminase (ALT) ≤ 3 times the upper limit of normal (ULN).
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- A serum creatinine concentration ≤ 2 x ULN
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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
- Clinically significant bleeding within 4 weeks of screening defined as any grade 3 or grade 4 bleeding by WHO Bleeding Scale or any gastrointestinal (GI) bleeding or intracranial hemorrhage
- Splenic enlargement extending >8 cm below the left costal margin
- Myelodysplastic syndrome with fibrosis (MF 3)
- Received Anti-Thymocyte Globulin (ATG) within 6 months of screening
- Received immunomodulating agents, histone deacetylase inhibitors, cyclosporine, or mycophenolate within 4 weeks of screening
- History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
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- Concurrent use of granulocyte colony-stimulating factor (G-CSF) except for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents or corticosteroids that were being administered prior to screening are allowed.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- Pregnant or breast feeding
- Current alcohol or drug abuse
- Known Hepatitis B or Hepatitis C infection or liver cirrhosis
- Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- At eltrombopag dose levels 200 mg and above cohorts, participants with a QT corrected for heart rate (QTc) > 480 msec at screening, if other drugs known to cause prolonged QT are stopped an EKG documenting QTc below 480 msec is required.
- History of metastatic malignancy in the preceding 2 years
- Known Human Immunodeficiency Virus (HIV) positive patients. These patients are excluded because they may have morphologic dysplasia which mimics MDS but is not true MDS Tand thrombocytopenia could be multifactorial secondary to HIV infection or to medications.
- Receiving, or planning to receive, any of the medications listed in the Prohibited Medications section during conduct of the study.
- East Asian patients (Chinese, Japanese, Taiwanese, and Korean ancestry) are excluded during stage I of the study (dose escalation phase) due to the different pharmacogenomics in this patient population.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Eltrombopag in Myelodysplastic Syndrome (MDS) Patients With Thrombocytopenia Who Progressed or Are Resistant to Hypomethylating Agents
The purpose of this study is to evaluate the safety and efficacy of eltrombopag in people who have myelodysplastic syndrome (MDS) with thrombocytopenia who have progressed or are resistant to decitabine or azacitidine. (These are the only 2 drugs approved by the U.S. Food and Drug Administration [FDA] which can improve platelet counts). The investigators (the study doctor, study staff, and sponsor) want to find out what effects, good or bad, eltrombopag (study drug) may have on people with low platelet counts due to MDS. The investigators will also be testing how well eltrombopag may work at different doses in these diseases.
Read the detailed description
Study was originally designed as a Phase I/II but was terminated during the Phase I portion due to lack of efficacy
- Conditions
- Myelodysplastic Syndrome (MDS), Thrombocytopenia
- Being tested
- Eltrombopag
- Keywords
- platelets
- Medical subject headings
- Myelodysplastic Syndromes, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Also called Promacta®
In Stage 1 the best dose of eltrombopag will be found to take into Stage 2, which will treat 15 participants at this dose.
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag Treatment | Experimental | Phase I: Dose Escalation Receives: Drug: Eltrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Determine the maximum tolerated dose (MTD) of eltrombopag for the treatment of thrombocytopenia in participants with MDS who have either progressed or are resistant to Hypomethylating Agents (HMTA). The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2011 (estimated)
- Study start6 Apr 2011
- Primary completion3 Nov 2017
- Study completion3 Nov 2018
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- 37 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Rami Komrokji, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01286038
- Sponsor's protocol ID
- MCC-16523
- Status last verified
- Nov 2022
- First submitted
- 27 Jan 2011
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Eltrombopag in Myelodysplastic Syndrome (MDS) Patients With Thrombocytopenia Who Progressed or Are Resistant to Hypomethylating Agents
- ClinicalTrials.gov ID
- NCT01286038
- Acronym / sponsor ID
- MCC-16523
- Conditions
- Myelodysplastic Syndrome (MDS), Thrombocytopenia
- Keywords
- platelets
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 37 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 6 Apr 2011 (actual)
- Primary completion
- 3 Nov 2017 (actual)
- Study completion
- 3 Nov 2018 (actual)
- First posted
- 31 Jan 2011 (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 purpose of this study is to evaluate the safety and efficacy of eltrombopag in people who have myelodysplastic syndrome (MDS) with thrombocytopenia who have progressed or are resistant to decitabine or azacitidine. (These are the only 2 drugs approved by the U.S. Food and Drug Administration [FDA] which can improve platelet counts). The investigators (the study doctor, study staff, and sponsor) want to find out what effects, good or bad, eltrombopag (study drug) may have on people with low platelet counts due to MDS. The investigators will also be testing how well eltrombopag may work at different doses in these diseases.
Detailed description
Study was originally designed as a Phase I/II but was terminated during the Phase I portion due to lack of efficacy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag Treatment | Experimental | Drug: EltrombopagPhase I: Dose Escalation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Confirmed diagnosis of MDS using the World Health Organization (WHO) classification or a diagnosis of WHO Myelodysplastic/ Myeloproliferative Neoplasm (MDS/MPN) or MDS refractory anemia with excess blast in transformation (RAEB-t) by French American British (FAB) classification (AML with 20-30% myeloblasts by WHO classification).
- All prognostic risk groups according to the International Prognostic Scoring System (IPSS) and MD Anderson Risk Model
- At least one prior HMTA treatment with either azacitidine or decitabine and subsequent loss of response to HMTA, progression while on HMTA, or no response to HMTA, defined as failure to achieve at least HI after 4 cycles of treatment
- The mean of the two platelet counts taken within 1 month prior to dosing must be ≤50 x 10^9/L. Platelets counts must reflect pre-transfusion trough results or be obtained no sooner than 1 week after platelet transfusion to assure stable baseline platelet count. The platelet count obtained should be outside the expected nadir of prior therapies.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >60%
Key exclusion criteria (17 listed)
- Clinically significant bleeding within 4 weeks of screening defined as any grade 3 or grade 4 bleeding by WHO Bleeding Scale or any gastrointestinal (GI) bleeding or intracranial hemorrhage
- Splenic enlargement extending >8 cm below the left costal margin
- Myelodysplastic syndrome with fibrosis (MF 3)
- Received Anti-Thymocyte Globulin (ATG) within 6 months of screening
- Received immunomodulating agents, histone deacetylase inhibitors, cyclosporine, or mycophenolate within 4 weeks of screening
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 |
|---|---|---|
| EltrombopagAlso: Promacta®In Stage 1 the best dose of eltrombopag will be found to take into Stage 2, which will treat 15 participants at this dose. | Drug | Eltrombopag Treatment |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 24 months
Determine the maximum tolerated dose (MTD) of eltrombopag for the treatment of thrombocytopenia in participants with MDS who have either progressed or are resistant to Hypomethylating Agents (HMTA). The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT).
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
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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.
Rami Komrokji, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 Eltrombopag in people with Myelodysplastic Syndrome (MDS) and Thrombocytopenia, run by H. Lee Moffitt Cancer Center and Research Institute 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 9 inclusion and 17 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: stopped early, as of the sponsor's last update on 7 Nov 2022. 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 was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
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) (time frame: 24 months). 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 7 Nov 2022.