Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

Official title:

A Phase 2 Randomized Double-Blind Placebo-Controlled Study of Pracinostat in Combination With Azacitidine in Patients With Previously Untreated International Prognostic Scoring System (IPSS) Intermediate Risk-2 or High-Risk Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01873703
• Other study ID #: MEI-003
• Status: Completed
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: November 2016

Study information

• Verified date: September 2018
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this randomized, double-blind, placebo-controlled study is to determine the safety and efficacy of pracinostat compared to placebo when combined with azacitidine, and FDA approved treatment for Myelodysplastic Syndrome (MDS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: November 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Voluntary written informed consent

• Histologically or cytologically documented diagnosis of MDS (any French-American-British [FAB] classification subtype; that is classified as intermediate 2 (1.5 to 2.0 points) or high risk (=2.5 points) according to the International Prognostic Scoring System risk category, with >5% and <30% blasts, and a peripheral blast count of <20,000

• Bone marrow aspirate smears and bone marrow biopsies within 28 days of first study treatment

• There must be a clinical indication for treatment with azacitidine.

• Previously untreated with hypomethylating agents (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed)

• Eastern Cooperative Oncology Group performance status of 0, 1, or 2

• Adequate organ function as evidenced by:

1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x the upper limit of normal (ULN) (=5 x ULN for patients with hepatic metastases

2. Total bilirubin =1.5 x ULN or total bilirubin of 2, whichever is higher

3. Serum creatinine <2 mg/dL, or creatinine clearance =1.5 x ULN

4. QTcF interval =470 msec

• Female or male patients =18 years-of-age

• Male patients who are surgically sterile or willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period

• Female patients who are surgically sterile or post menopausal or female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from intercourse during the study treatment period, who are not breastfeeding, and who have had a negative serum pregnancy test =7 days prior to first study treatment.

• Willingness and ability to comply with the trial and follow-up procedures

Exclusion Criteria:

• Received any of the following within the specified time frame prior to administration of study medication:

1. Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer

2. Previous therapy for malignancy within 21 days prior to first study treatment, including any chemotherapy, immunotherapy, biological or hormonal therapy (6 weeks for nitrosoureas or mitomycin C)

3. Hydroxyurea within 48 hours prior to first study treatment

4. Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists at least 7 days (14 days for Aranesp) prior to study enrollment

5. Major surgery within 4 weeks prior to first study treatment

• Patients that have not recovered from side effects of previous therapy

• Cardiopulmonary function exclusion:

1. Current unstable arrhythmia requiring treatment

2. History of symptomatic congestive heart failure (New York Heart Association Classes III or IV)

3. History of myocardial infarction within 6 months of enrollment

4. Current unstable angina

• Concomitant treatment with histone deacetylase (HDAC) inhibitors or drugs with significant action as HDAC inhibitors, such as valproic acid, is not permitted

• Clinical evidence of central nervous system involvement

• Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).

• Active infection with HIV or chronic hepatitis B or C

• Life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study

• 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

• Inability (including psychological, familial, sociological, or geographical conditions) to comply with trial and/or follow-up procedures

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• pracinostat
Histone deacetylase inhibitor (HDACi)
• Placebo
Placebo
• Azacitidine
Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer at Johns Hopkins	Baltimore	Maryland
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Florida Cancer Specialists South	Fort Myers	Florida
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Ctr	Indianapolis	Indiana
United States	Scripps Cancer Center	La Jolla	California
United States	Michigan State University	Lansing	Michigan
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Southern Cancer Center	Mobile	Alabama
United States	Sarah Cannon Cancer Center, Tennessee Oncology	Nashville	Tennessee
United States	Weill Cornell Medical Center	New York	New York
United States	Nebraska Methodist	Omaha	Nebraska
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Swedish Cancer Institute	Seattle	Washington
United States	Florida Cancer Specialist and Research Institute	Tallahassee	Florida
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate efficacy	Estimate the relative efficacy, measured by complete remission rate of treatment wiht pracinostat plus azacitidine versus placebo plus azacitidine	6 months
Secondary	Overall response rate	Estimate the overall response rate [ORR = CR + complete remission + partial response (PR)]	6 months
Secondary	Hematologic Improvement	Estimate the overall hematologic improvement (HI) response rate by review of hematologic lab values each cycle including bone marrow blast counts, platelets and erythrocytes.	6 months
Secondary	Duration of response	Estimate the duration of response	6 months
Secondary	Progression free survival	Estimate the progression-free survival (PFS) duration of pracinostat plus azacitidine and the relative benefit of that combination versus placebo plus azacitidine as assessed by the PFS hazard ratio	12 months
Secondary	Rate of leukemic transformation	Estimate the rate of leukemic transformation at landmark time points (6 months, 12 months, 18 months, and 24 months) using clinical review of hematologic lab counts each cycle	6 - 24 months
Secondary	Overall survival	Estimate the overall survival (OS) duration of pracinostat plus azacitidine and the relative benefit of that combination versus placebo plus azacitidine as assessed by the OS hazard ratio	6-24 months
Secondary	AE profile	Assess the adverse event (AE) profile of pracinostat and placebo when combined with azacitidine by clinical review of safety events by grade, relationship and event outcomes.	12 months

External Links

•   Sponsor website