MDSPhase 2NCT00321711
Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents
A Phase 2 study testing AMG 531 (Romiplostim), Azacitidine and Decitabine in people with MDS and Myelodysplastic Syndromes, run by Amgen.
Trial summary
The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDS, Myelodysplastic Syndromes, Thrombocytopenia
- What is being tested?
- AMG 531 (Romiplostim), Azacitidine and Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2006to 19 Oct 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Inclusion Criteria: - Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification - Low, Intermediate-1 or Intermediate-2 risk category MDS using the IPSS (International Prognostic Scoring System) - Planned to receive either azacytidine 75 mg/m2 by subcutaneous administration each day for 7 days or decitabine 20 mg/m2 by intravenous administration each day for 5 days for at least 4 cycles Exclusion Criteria:
- Prior exposure to >3 cycles hypomethylating agents
- Prior history of leukemia or aplastic anemia
- Prior history of bone marrow transplantation
- Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ³ 3 years before randomization
- Active or uncontrolled infections
- Unstable angina, congestive heart failure [NYHA (New York Heart Association) > class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
- History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past year
- History of venous thrombosis that currently requires anti-coagulation therapy
- Received IL-11 within 4 weeks of screening
- Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
- Have previously received any other thrombopoietic growth factor
About this study
Official title: A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim (AMG 531) Treatment of Subjects With Low or Intermediate Risk Myelodysplastic Syndrome (MDS) Receiving Hypomethylating Agents
The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.
- Conditions
- MDS, Myelodysplastic Syndromes, Thrombocytopenia
- Being tested
- Placebo, AMG 531 (Romiplostim), Azacitidine, Decitabine
- Keywords
- MDS, Myelodysplastic Syndromes, Refractory Cytopenias, Thrombocytopenia
- Medical subject headings
- Myelodysplastic Syndromes, Thrombocytopenia, Cytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.
AMG 531 (Romiplostim)Biological
AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.
AzacitidineDrug
hypomethylating agent
DecitabineDrug
hypomethylating agent
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 500 AMG 531 (Part A - azacitidine) | Active comparator | 500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles Receives: Biological: AMG 531 (Romiplostim); Drug: Azacitidine |
| Dose level 1 750 AMG 531 (Part B - decitabine) | Active comparator | 750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles Receives: Biological: AMG 531 (Romiplostim); Drug: Decitabine |
| Dose level 2 750 AMG 531 (Part A - azacitidine) | Active comparator | 750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles Receives: Biological: AMG 531 (Romiplostim); Drug: Azacitidine |
| Placebo (Part A - azacitidine) | Placebo comparator | Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles Receives: Drug: Placebo; Drug: Azacitidine |
| Placebo (Part B - decitabine) | Placebo comparator | Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles Receives: Drug: Placebo; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of a Clinically Significant Thrombocytopenic Event
Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.
Measured: Treatment period (up to 20 weeks)
Secondary outcomes (3)
Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia
Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia
Measured: Treatment period (up to 20 weeks)
Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period
CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10^9/L, neutrophils ≥ 1x10^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.
Measured: Treatment period (up to 20 weeks)
Platelet Transfusion
Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)
Measured: Study day 1 through the interim follow-up visit (up to 20 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2006 (estimated)
- Study start1 Oct 2006
- Primary completion19 Oct 2009
- Study completion19 Oct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MDSStudies of the same condition, open and under way.
- More trials run by AmgenThe 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 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00321711
- Sponsor's protocol ID
- 20050232
- Status last verified
- Sep 2018
- First submitted
- 2 May 2006
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Greenberg PL, Garcia-Manero G, Moore M, Damon L, Roboz G, Hu K, Yang AS, Franklin J. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine. Leuk Lymphoma. 2013 Feb;54(2):321-8. doi: 10.3109/10428194.2012.713477. Epub 2012 Nov 15.
PubMed 22906162Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010 Oct 28;116(17):3163-70. doi: 10.1182/blood-2010-03-274753. Epub 2010 Jul 14.
PubMed 20631375
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim (AMG 531) Treatment of Subjects With Low or Intermediate Risk Myelodysplastic Syndrome (MDS) Receiving Hypomethylating Agents
- ClinicalTrials.gov ID
- NCT00321711
- Acronym / sponsor ID
- 20050232
- Conditions
- MDS, Myelodysplastic Syndromes, Thrombocytopenia
- Keywords
- MDS, Myelodysplastic Syndromes, Refractory Cytopenias, Thrombocytopenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2006 (actual)
- Primary completion
- 19 Oct 2009 (actual)
- Study completion
- 19 Oct 2009 (actual)
- First posted
- 4 May 2006 (estimated)
- Results
- Posted 5 Apr 2011
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 effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 500 AMG 531 (Part A - azacitidine) | Active comparator | Biological: AMG 531 (Romiplostim), Drug: Azacitidine500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
| Dose level 1 750 AMG 531 (Part B - decitabine) | Active comparator | Biological: AMG 531 (Romiplostim), Drug: Decitabine750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles |
| Dose level 2 750 AMG 531 (Part A - azacitidine) | Active comparator | Biological: AMG 531 (Romiplostim), Drug: Azacitidine750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
| Placebo (Part A - azacitidine) | Placebo comparator | Drug: Placebo, Drug: AzacitidinePlacebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles |
| Placebo (Part B - decitabine) | Placebo comparator | Drug: Placebo, Drug: DecitabinePlacebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| PlaceboSubjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period. | Drug | Placebo (Part A - azacitidine), Placebo (Part B - decitabine) |
| AMG 531 (Romiplostim)AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization. | Biological | Dose level 1 500 AMG 531 (Part A - azacitidine), Dose level 1 750 AMG 531 (Part B - decitabine), Dose level 2 750 AMG 531 (Part A - azacitidine) |
| Azacitidinehypomethylating agent | Drug | Dose level 1 500 AMG 531 (Part A - azacitidine), Dose level 2 750 AMG 531 (Part A - azacitidine), Placebo (Part A - azacitidine) |
| Decitabinehypomethylating agent | Drug | Dose level 1 750 AMG 531 (Part B - decitabine), Placebo (Part B - decitabine) |
Primary outcome
Occurrence of a Clinically Significant Thrombocytopenic Event
Time frame: Treatment period (up to 20 weeks)
Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.
3 secondary outcomes
Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia
Time frame: Treatment period (up to 20 weeks)
Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period
Time frame: Treatment period (up to 20 weeks)
Platelet Transfusion
Time frame: Study day 1 through the interim follow-up visit (up to 20 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22906162Greenberg PL, Garcia-Manero G, Moore M, Damon L, Roboz G, Hu K, Yang AS, Franklin J. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine. Leuk Lymphoma. 2013 Feb;54(2):321-8. doi: 10.3109/10428194.2012.713477. Epub 2012 Nov 15.
- Background: PubMed 20631375Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010 Oct 28;116(17):3163-70. doi: 10.1182/blood-2010-03-274753. Epub 2010 Jul 14.
- AmgenTrials clinical trials 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.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AMG 531 (Romiplostim), Azacitidine and Decitabine in people with MDS and Myelodysplastic Syndromes, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurrence of a Clinically Significant Thrombocytopenic Event (time frame: Treatment period (up to 20 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00321711, which also lists 2 linked publications.
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 17 Oct 2018.