Myelodysplastic SyndromesPhase 2NCT00384956
A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes
A Phase 2 study testing Azacitidine in people with Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Mar 2010
- 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
Who may be able to join
- Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:
- Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion
- Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
- Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL.
- ECOG performance status of 0-2.
- Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
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- Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).
- Life expectancy of at least 12 weeks.
- Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities.
- Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
- Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial.
- Men must be willing to avoid fathering a new child while receiving therapy with azacitidine.
- ≥18 years, no upper age limit
- Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation.
Who cannot join
- Known CNS leukemia.
- Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
- Known or suspected hypersensitivity to azacitidine or mannitol.
- Receiving any other investigational agents within 30 days of first dose of study drug.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Known positive serology for HIV.
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- Had radiotherapy within 14 days prior to study enrollment.
- Known presence of hepatic tumors.
- <18 years of age
- Exclude women who are pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection.
Read the detailed description
Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.
The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Azacitidine
- Keywords
- MDS either de novo or secondary, fitting any of the WHO classifications.
- Medical subject headings
- Myelodysplastic Syndromes, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5-azacitidine, Vidaza
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine | Experimental | Azacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle. Patients that do not respond after two cycles will have the dose increased to 100 mg/m2. Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle. Individuals who demonstrate a loss of response will resume 28 day cycles. Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Remission (CR) and Partial Remission (PR)
Defined according to the modified International Working Group (IWG) (2006) response criteria for myelodysplasia:
CR=bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L. Residual dysplasia was allowed.
PR= All of the CR criteria if abnormal before treatment except: bone marrow blasts decreased by ≥50% over pretreatment but still >5%.
Measured: After 4 cycles of therapy (up to 112 days after start of treatment)
Secondary outcomes (5)
Rate of Hematologic Improvement
International Working Group (IWG) for Myelodysplasia (MDS).
Measured: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Transfusion Independence
Measured: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Cytogenetic Response
Measured: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Overall Survival
Overall survival is defined as the date of first dose of study drug to the date of death from any cause.
Measured: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.
Measured: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startAug 2006
- Primary completionAug 2008
- Study completionMar 2010
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.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ravi Vij, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384956
- Sponsor's protocol ID
- 06-0585
- Status last verified
- Oct 2016
- First submitted
- 4 Oct 2006
- Last updated
- 12 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00384956
- Acronym / sponsor ID
- 06-0585
- Conditions
- Myelodysplastic Syndromes
- Keywords
- MDS either de novo or secondary, fitting any of the WHO classifications.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 6 Oct 2006 (estimated)
- Results
- Posted 8 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection.
Detailed description
Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.
The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine | Experimental | Drug: AzacitidineAzacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle. Patients that do not respond after two cycles will have the dose increased to 100 mg/m2. Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle. Individuals who demonstrate a loss of response will resume 28 day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:
- ECOG performance status of 0-2.
- Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
- Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).
- Life expectancy of at least 12 weeks.
Key exclusion criteria (10 listed)
- Known CNS leukemia.
- Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
- Known or suspected hypersensitivity to azacitidine or mannitol.
- Receiving any other investigational agents within 30 days of first dose of study drug.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
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 |
|---|---|---|
| AzacitidineAlso: 5-azacitidine, Vidaza | Drug | Azacitidine |
Primary outcome
Rate of Complete Remission (CR) and Partial Remission (PR)
Time frame: After 4 cycles of therapy (up to 112 days after start of treatment)
Defined according to the modified International Working Group (IWG) (2006) response criteria for myelodysplasia: CR=bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L. Residual dysplasia was allowed. PR= All of the CR criteria if abnormal before treatment except: bone marrow blasts decreased by ≥50% over pretreatment but still >5%.
5 secondary outcomes
Rate of Hematologic Improvement
Time frame: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Transfusion Independence
Time frame: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Cytogenetic Response
Time frame: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Overall Survival
Time frame: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.
Time frame: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
Related trials for Myelodysplastic Syndromes
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Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
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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.
Ravi Vij, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine in people with Myelodysplastic Syndromes, run by Washington University School of Medicine 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 14 inclusion and 10 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 12 Dec 2016. 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 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 8 Sep 2014). 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?
Rate of Complete Remission (CR) and Partial Remission (PR) (time frame: After 4 cycles of therapy (up to 112 days after start of treatment)). 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 12 Dec 2016.