Acute Myeloid LeukemiaPhase 2NCT01912274
Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
A Phase 2 study testing Pracinostat and Azacitidine in people with Acute Myeloid Leukemia, run by Helsinn Healthcare SA at 17 sites in United States.
Trial summary
The purpose of this study is to determine the safety and effectiveness of pracinostat when combined with azacitadine for patients who are 65 years of age or older and have Acute Myelogenous Leukemia (AML) Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Pracinostat and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 17 sitesUnited States
- Study dates
- 24 Dec 2013to 8 Nov 2016
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Male or female subjects aged ≥65 years.
- Voluntary written informed consent before performance of any study related procedure not part of normal medical care.
- Newly diagnosed de novo, secondary, or treatment-related AML with intermediate or unfavorable-risk cytogenetics based on the Southwest Oncology Group (SWOG) classifications (Slovak et al, 2000).
- One prior cycle of therapy with an approved hypomethylating agent (HMA) such as azacitidine or decitabine is allowed for either an antecedent hematologic disorder (AHD) or AML. Patients are also eligible if they have received lenolidamide, immunosuppressive therapy or low dose chemotherapy for their AHD. Prior hydroxyurea is allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- ≥20% blasts in bone marrow.
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- Peripheral WBC <30,000/uL.
- Adequate organ function as evidenced by:
- Total bilirubin 2x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)2.5x ULN
- Serum creatinine 2x ULN
- QT interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms) for male subjects or ≤470 ms for female subjects on ECG at Screening.
- Male subjects who are surgically sterile or willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period.
- Female subjects who are not of childbearing potential.
- Willingness and ability to understand the nature of this study and to comply with the study and follow up procedures
Who cannot join
- Acute promyelocytic leukemia (French-American-British [FAB] M3 classification).
- Known AML-associated t(15;17), t(8;21), t(16;16), del(16q), or inv(16) karyotype abnormalities.
- Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer. Other malignancies will be considered on a case-by-case basis.
- Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk.
- Uncontrolled or symptomatic arrhythmias, unstable angina, or any Class 3 or 4 cardiac diseases as defined by the New York Heart Association (NYHA) Functional Classification.
- Clinical evidence of central nervous system (CNS) involvement.
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- Are candidates for intensive chemotherapy (induction chemotherapy, bone marrow, or stem cell transplant) within the next 4 months.
- Received more than one prior cycle of HMA, previous bone marrow transplant or other intensive chemotherapy regimens for either an AHD or AML.
- Received prior radiation therapy for extramedullary disease within 2 weeks of study enrollment.
- Received prior histone deacetylase (HDAC) inhibitor or deacetylase (DAC) inhibitor is not permitted such as Istodax (romidepsin/depsipetide) or valproic acid.
- Received hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 7 days (14 days for Aranesp) prior to study enrollment.
- Have been treated with any chemotherapeutic agent within 2 weeks or 5 half-lives of the first dose of study drug, whichever is longer.
- Are being treated with systemic corticosteroids. Inhaled and topical steroids as well as intermittent dexamethasone for nausea or vomiting are permitted.
- Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
- Uncontrolled active systemic infections.
- Gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
- Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of study drugs, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the subject inappropriate for this study.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Emory University
Atlanta, Georgia, 30322
Cooper Hospital
Camden, New Jersey, 08103
Medical College of South Carolina-Hollings Cancer Ctr
Charleston, South Carolina, 29425
The University of Chicago
Chicago, Illinois, 60637
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390-9179
City of Hope Comprehensive Cancer Ctr
Duarte, California, 91010
MD Anderson
Houston, Texas, 77030
Inidana Univ Simon Cancer Center
Indianapolis, Indiana, 46202
USC Norrris Cancer Center
Los Angeles, California, 90033
Medical College of Wisconsin-Froedtert Cancer Center
Milwaukee, Wisconsin, 53226
University of Nebraska Medical Center
Omaha, Nebraska, 68198-7680
Bay Area Cancer Research Group
Pleasant Hill, California, 94523
Oregon Health and Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Mercy Medical Research Center
Springfield, Missouri, 65807
Stanford University School of Medicine
Stanford, California, 94305-5821
University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase II Open-Label, Single-arm, Two-Stage, Multicenter Trial of Pracinostat in Combination With Azacitidine in Elderly (Age 65 Years or Older) Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The purpose of this study is to determine the safety and effectiveness of pracinostat when combined with azacitadine for patients who are 65 years of age or older and have Acute Myelogenous Leukemia (AML)
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Pracinostat, Azacitidine
- Keywords
- AML, open label, nonrandomized, single arm, elderly patients, HMA, newly diagnosed
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PracinostatDrug
Also called SB939
Elderly newly diagnosed patients will all receive pracinostat
AzacitidineDrug
Also called Vidaza
Elderly newly diagnosed patients will all receive azacitadine
| Study group | Role | What they receive |
|---|---|---|
| Pracinostat with azacitadine | Experimental | 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Receives: Drug: Pracinostat; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Response Rate
Proportion of patients assessed as having achieved a disease response of either CR or CRi or MLFS according to the IWG criteria. CR (ie, complete remission defined as <5% blasts in the bone marrow, no blasts with Auer rods, no extramedullary disease, ANC ≥1000/μL, and platelets ≥100,000/μL must be independent of transfusions for at least 1 week before each assessment).
CRi (ie, morphologic complete remission with incomplete blood count recovery, defined as morphologic CR with residual neutropenia (<1,000/μL) or residual thrombocytopenia (<100,000/μL), no extramedullary disease, does not require transfusion independence) MLFS (ie, morphologic leukemia free state, defined as <5% blasts in an aspirate sample with marrow spicules, no extramedullary disease, does not require transfusion independence)
Measured: through study completion up to a maximum of three years
Secondary outcomes (6)
Overall Response Rate
proportion of patients with CR plus CRi plus MLFS plus PR plus PRi
Measured: through study completion up to a maximum of three years
Complete Cytogenetic Response Plus Molecular Complete Remission
proportion of patients assessed as having complete cytogenetic response (CRc) + molecular complete remission (CRm) to pracinostat plus azacitidine
Measured: through study completion up to a maximum of three years
Progression Free Survival
time from the first day of study administration to PD, relapse from CR/CRi/MLFS, lack of efficacy or death.
Measured: through study completion up to a maximum of three years
Overall Survival
time from the first day of study drug administration to death
Measured: through study completion up to a maximum of three years
Duration of Best Response
The duration of the best response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.
Measured: through study completion up to a maximum of 3 years
Duration of Response
The duration of the response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, PR, PRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.
Measured: through study completion up to a maximum of three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2013 (estimated)
- Study start24 Dec 2013
- Primary completion8 Nov 2016
- Study completion8 Nov 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinn Healthcare SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01912274
- Sponsor's protocol ID
- MEI-004
- Status last verified
- Jan 2021
- First submitted
- 29 Jul 2013
- Last updated
- 9 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Garcia-Manero G, Abaza Y, Takahashi K, Medeiros BC, Arellano M, Khaled SK, Patnaik M, Odenike O, Sayar H, Tummala M, Patel P, Maness-Harris L, Stuart R, Traer E, Karamlou K, Yacoub A, Ghalie R, Giorgino R, Atallah E. Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study. Blood Adv. 2019 Feb 26;3(4):508-518. doi: 10.1182/bloodadvances.2018027409.
PubMed 30760466
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label, Single-arm, Two-Stage, Multicenter Trial of Pracinostat in Combination With Azacitidine in Elderly (Age 65 Years or Older) Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT01912274
- Acronym / sponsor ID
- MEI-004
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, open label, nonrandomized, single arm, elderly patients, HMA, newly diagnosed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Helsinn Healthcare SAIndustry (pharma, biotech, devices)
- Study start
- 24 Dec 2013 (actual)
- Primary completion
- 8 Nov 2016 (actual)
- Study completion
- 8 Nov 2016 (actual)
- First posted
- 31 Jul 2013 (estimated)
- Results
- Posted 9 Feb 2021
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 determine the safety and effectiveness of pracinostat when combined with azacitadine for patients who are 65 years of age or older and have Acute Myelogenous Leukemia (AML)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pracinostat with azacitadine | Experimental | Drug: Pracinostat, Drug: Azacitidine60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (15 listed)
- Male or female subjects aged ≥65 years.
- Voluntary written informed consent before performance of any study related procedure not part of normal medical care.
- Newly diagnosed de novo, secondary, or treatment-related AML with intermediate or unfavorable-risk cytogenetics based on the Southwest Oncology Group (SWOG) classifications (Slovak et al, 2000).
- One prior cycle of therapy with an approved hypomethylating agent (HMA) such as azacitidine or decitabine is allowed for either an antecedent hematologic disorder (AHD) or AML. Patients are also eligible if they have received lenolidamide, immunosuppressive therapy or low dose chemotherapy for their AHD. Prior hydroxyurea is allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Key exclusion criteria (17 listed)
- Acute promyelocytic leukemia (French-American-British [FAB] M3 classification).
- Known AML-associated t(15;17), t(8;21), t(16;16), del(16q), or inv(16) karyotype abnormalities.
- Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer. Other malignancies will be considered on a case-by-case basis.
- Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk.
- Uncontrolled or symptomatic arrhythmias, unstable angina, or any Class 3 or 4 cardiac diseases as defined by the New York Heart Association (NYHA) Functional Classification.
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 |
|---|---|---|
| PracinostatAlso: SB939Elderly newly diagnosed patients will all receive pracinostat | Drug | Pracinostat with azacitadine |
| AzacitidineAlso: VidazaElderly newly diagnosed patients will all receive azacitadine | Drug | Pracinostat with azacitadine |
Primary outcome
Best Response Rate
Time frame: through study completion up to a maximum of three years
Proportion of patients assessed as having achieved a disease response of either CR or CRi or MLFS according to the IWG criteria. CR (ie, complete remission defined as <5% blasts in the bone marrow, no blasts with Auer rods, no extramedullary disease, ANC ≥1000/μL, and platelets ≥100,000/μL must be independent of transfusions for at least 1 week before each assessment). CRi (ie, morphologic complete remission with incomplete blood count recovery, defined as morphologic CR with residual neutropenia (<1,000/μL) or residual thrombocytopenia (<100,000/μL), no extramedullary disease, does not require transfusion independence) MLFS (ie, morphologic leukemia free state, defined as <5% blasts in an aspirate sample with marrow spicules, no extramedullary disease, does not require transfusion independence)
6 secondary outcomes
Overall Response Rate
Time frame: through study completion up to a maximum of three years
Complete Cytogenetic Response Plus Molecular Complete Remission
Time frame: through study completion up to a maximum of three years
Progression Free Survival
Time frame: through study completion up to a maximum of three years
Overall Survival
Time frame: through study completion up to a maximum of three years
Duration of Best Response
Time frame: through study completion up to a maximum of 3 years
Duration of Response
Time frame: through study completion up to a maximum of three years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30760466Garcia-Manero G, Abaza Y, Takahashi K, Medeiros BC, Arellano M, Khaled SK, Patnaik M, Odenike O, Sayar H, Tummala M, Patel P, Maness-Harris L, Stuart R, Traer E, Karamlou K, Yacoub A, Ghalie R, Giorgino R, Atallah E. Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study. Blood Adv. 2019 Feb 26;3(4):508-518. doi: 10.1182/bloodadvances.2018027409.
- Sponsor 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.
Guillermo Garcia-Manero, MD principal investigator
M.D. Anderson Cancer Center
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pracinostat and Azacitidine in people with Acute Myeloid Leukemia, run by Helsinn Healthcare SA at 17 sites 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 15 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: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites 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 9 Feb 2021). 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?
Best Response Rate (time frame: through study completion up to a maximum of three years). 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 NCT01912274, which also lists 1 linked publication.
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 9 Feb 2021.