Myelodysplastic SyndromePhase 1NMDSG10ANCT01481220
Safety Study of Eltrombopag Combined With Azacitidine to Treat Myelodysplastic Syndrome (MDS)
A Phase 1 study testing Eltrombopag in people with Myelodysplastic Syndrome and Thrombocytopenia, run by Nordic MDS Group at 1 site in Sweden.
Trial summary
Patients with Myelodysplastic Syndromes (MDS) often suffer from low platelet levels which may lead to bleeding complications. Treatment with cytotoxic agents can decrease the platelet levels further. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Thrombocytopenia
- What is being tested?
- Eltrombopag
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSweden
- Study dates
- Oct 2011to May 2013
- 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
- Adult subjects (18 years of age or older) with advanced MDS or sAML/MDS requiring treatment with Azacitidine as approved by EMEA:
- MDS classified as Intermediate 2-risk or high risk according to the international prognostic scoring system (IPSS) or
- Chronic myelomonocytic leukaemia (CMML) with 10-29% bone marrow blasts without myeloproliferative disease or
- Acute myeloblastic leukaemia (AML) with 20-30% bone marrow blasts with multilineage dysplasia according to the WHO classification.
- Platelet counts < 75 x 109 /L at start of Azacitidine treatment.
- Subjects must have platelet count and platelet transfusion data available over a period of 4 weeks prior to inclusion.
Show all 22Show fewer
- During the 8 weeks prior to inclusion in study, subjects must have a baseline bone marrow examination including all of the following:
- cytomorphology to confirm bone marrow blasts
- cytogenetics
- ECOG Status 0-2.
- Subject is able to understand and comply with protocol requirements and instructions.
- Subject has signed and dated informed consent.
- Adequate baseline organ function defined by the criteria below:
- total bilirubin (except for Gilbert's Syndrome) </= 1.5xULN
- ALT and AST </= 3xULN
- creatinine </= 2.5 xULN
- Subject is practicing an acceptable method of contraception (documented in CRF).Female subjects (or female partners of male subjects) must either be of non childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use 1 of the following highly effective methods of contraception (i.e., Pearl Index < 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
- Complete abstinence from intercourse;
- Intrauterine device (IUD);
- Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
- Male partner is sterile prior to entry into the study and is the only partner of the female;
- Systemic contraceptives (combined or progesterone only).
Who cannot join
- Subjects with a diagnosis of acute promyelocytic leukemia.
- Patients with short life expectancy (less than 3 months)
- Patients with bone marrow fibrosis that does not allow bone marrow aspiration (so-called "dry tap") or fibrosis grade II or III (grading according to European consensus on grading bone marrow fibrosis.
- History of treatment for cancer other than MDS or sAML/MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.
- Patients with clinically significant splenomegaly, or > 16 cm spleen in length measured by ultrasound
- Patients with known liver cirrhosis
Show all 15Show fewer
- Patients with East Asian ancestry such as Chinese, Japanese, Taiwanese or Korean.
- History of treatment with romiplostim or other TPO-R agonists.
- subjects with a QTc > 450 msec (QTc > 480 msec for subjects with Bundle Branch Block).
- Subjects with known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
- Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotropin [B-hCG] pregnancy test) at screening or pre-dose on Day 1.
- Current alcohol or drug abuse.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- Active and uncontrolled infections.
- Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Phase I Dose Finding Safety Study of a Thrombopoietin-receptor Agonist, Eltrombopag, in Patients With Myelodysplastic Syndrome Treated With Azacitidine
Patients with Myelodysplastic Syndromes (MDS) often suffer from low platelet levels which may lead to bleeding complications. Treatment with cytotoxic agents can decrease the platelet levels further. Eltrombopag is a relatively new drug that increases the platelet level in the blood by working directly on the bone marrow. It is available for treatment of the disease Immunological Thrombocytopenic Purpura (ITP). In this study patients with MDS and low platelet levels that are treated with the cytotoxic agent Azacitidine will also receive Eltrombopag. The administration of Eltrombopag to MDS patients treated with Azacitidine may result in less dose reductions and less treatment delays for Azacitidine and may reduce the need for thrombocyte transfusions and lower the risk of bleeding complications.
This is a phase I study, meaning that our major goal is to investigate the safety and tolerability for Eltrombopag in this patient group. It will also generate a basis for a phase II-III-study.
- Conditions
- Myelodysplastic Syndrome, Thrombocytopenia
- Being tested
- Eltrombopag
- Keywords
- Myelodysplastic syndrome, azacitidine, Eltrombopag, Thrombopoietin-receptor agonist, Thrombocytopenia, Transfusion dependency, Safety study
- 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
In this study 4 different doses of oral eltrombopag (50mg, 100mg, 200mg and 300mg) will be tested. A modified 3+3 patient cohorts design will be used so no new patients are accepted to start on a higher dose without prior tolerance at the previous dose. Patients will be given eltrombopag once daily starting one week before the start of azacitidine treatment and then continue throughout the study, which duration will be approximately 3 months (three Azacytidine cycles). Patients will be evaluated continuously by clinical and laboratory assessments as well as bone marrow examinations during the treatment period until 4 weeks after discontinuation of Eltrombopag. Response, AEs/SAEs and DLTs will be monitored throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine + Eltrombopag | Experimental | Not described Receives: Drug: Eltrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability parameters
Including:
- Non-hematological clinical, laboratory Grade 3/Grade 4 toxicities
- Change in bone marrow or peripheral blood blast counts from baseline
- Adverse events and interactions at increasing doses of eltrombopag
Measured: week 26
Secondary outcomes (4)
Azacitidine treatment delays and dose reductions
Measured: week 26
Need for thrombocyte transfusions
Measured: week 26
Bleeding complications
Measured: week 26
Possible signs of antineoplastic effects (blood values and bone marrow picture)
Measured: week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordic MDS Group
- Sponsor type
- Research network
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Tobias Svensson, M.D., Study director, Nordic MDS Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01481220
- Sponsor's protocol ID
- 2010-023663-18
- Acronym
- NMDSG10A
- Status last verified
- May 2013
- First submitted
- 17 Nov 2011
- Last updated
- 3 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase I Dose Finding Safety Study of a Thrombopoietin-receptor Agonist, Eltrombopag, in Patients With Myelodysplastic Syndrome Treated With Azacitidine
- ClinicalTrials.gov ID
- NCT01481220
- Acronym / sponsor ID
- NMDSG10A / 2010-023663-18
- Conditions
- Myelodysplastic Syndrome, Thrombocytopenia
- Keywords
- Myelodysplastic syndrome, azacitidine, Eltrombopag, Thrombopoietin-receptor agonist, Thrombocytopenia, Transfusion dependency, Safety study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Nordic MDS GroupResearch network
- Collaborators
- GlaxoSmithKline
- Study start
- Oct 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 29 Nov 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.
Patients with Myelodysplastic Syndromes (MDS) often suffer from low platelet levels which may lead to bleeding complications. Treatment with cytotoxic agents can decrease the platelet levels further. Eltrombopag is a relatively new drug that increases the platelet level in the blood by working directly on the bone marrow. It is available for treatment of the disease Immunological Thrombocytopenic Purpura (ITP). In this study patients with MDS and low platelet levels that are treated with the cytotoxic agent Azacitidine will also receive Eltrombopag. The administration of Eltrombopag to MDS patients treated with Azacitidine may result in less dose reductions and less treatment delays for Azacitidine and may reduce the need for thrombocyte transfusions and lower the risk of bleeding complications.
This is a phase I study, meaning that our major goal is to investigate the safety and tolerability for Eltrombopag in this patient group. It will also generate a basis for a phase II-III-study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine + Eltrombopag | Experimental | Drug: Eltrombopag |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Adult subjects (18 years of age or older) with advanced MDS or sAML/MDS requiring treatment with Azacitidine as approved by EMEA:
- Platelet counts < 75 x 109 /L at start of Azacitidine treatment.
- Subjects must have platelet count and platelet transfusion data available over a period of 4 weeks prior to inclusion.
- During the 8 weeks prior to inclusion in study, subjects must have a baseline bone marrow examination including all of the following:
- ECOG Status 0-2.
Key exclusion criteria (15 listed)
- Subjects with a diagnosis of acute promyelocytic leukemia.
- Patients with short life expectancy (less than 3 months)
- Patients with bone marrow fibrosis that does not allow bone marrow aspiration (so-called "dry tap") or fibrosis grade II or III (grading according to European consensus on grading bone marrow fibrosis.
- History of treatment for cancer other than MDS or sAML/MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.
- Patients with clinically significant splenomegaly, or > 16 cm spleen in length measured by ultrasound
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 |
|---|---|---|
| EltrombopagIn this study 4 different doses of oral eltrombopag (50mg, 100mg, 200mg and 300mg) will be tested. A modified 3+3 patient cohorts design will be used so no new patients are accepted to start on a higher dose without prior tolerance at the previous dose. Patients will be given eltrombopag once daily starting one week before the start of azacitidine treatment and then continue throughout the study, which duration will be approximately 3 months (three Azacytidine cycles). Patients will be evaluated continuously by clinical and laboratory assessments as well as bone marrow examinations during the treatment period until 4 weeks after discontinuation of Eltrombopag. Response, AEs/SAEs and DLTs will be monitored throughout the study. | Drug | Azacitidine + Eltrombopag |
Primary outcome
Safety and tolerability parameters
Time frame: week 26
Including: * Non-hematological clinical, laboratory Grade 3/Grade 4 toxicities * Change in bone marrow or peripheral blood blast counts from baseline * Adverse events and interactions at increasing doses of eltrombopag
4 secondary outcomes
Azacitidine treatment delays and dose reductions
Time frame: week 26
Need for thrombocyte transfusions
Time frame: week 26
Bleeding complications
Time frame: week 26
Possible signs of antineoplastic effects (blood values and bone marrow picture)
Time frame: week 26
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 3 May 2013.
Related trials for Myelodysplastic Syndrome
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Tobias Svensson, M.D. study director
Nordic MDS Group
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 and Thrombocytopenia, run by Nordic MDS Group at 1 site in Sweden.
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 22 inclusion and 15 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 3 May 2013. 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 Sweden. 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?
Safety and tolerability parameters (time frame: week 26). 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 3 May 2013.