Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA

NCT01993641 | Completed Phase 2

• 1 other identifier: MEI-005
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this open label study is to determine whether combining pracinostat (study drug) with Vidaza (azacitidine) or Dacogen (decitabine) will improve clinical responses in Myelodysplastic Syndrome (MDS) patients who have failed an initial single agent hypomethylating agent (HMA), and to provide additional safety and efficacy data.

Conditions

Myelodysplastic Syndrome; MDS

Keywords

Myelodysplastic Syndrome; MDS; pracinostat; Hypomethylating Agent; HMA; azacitadine; Vidaza; decitabine; dacogen

Outcome Measures

Primary Outcomes (1)

• Estimate clinical improvement

  Clinical Improvement Rate defined as the proportion of patients with CR, Marrow CR, PR, and HI.

  6 months

Secondary Outcomes (12)

• Estimate Overall Response Rate (ORR), including all Complete and Partial Responses, Marrow CR, HI, SD, transfusion independence, and cytogenetic responses

  6 months

• Estimate Complete Response (CR) rate

  6 months

• Estimate Hematologic Improvement (HI) rate

  6 months

• Estimate Duration of Response (DoR)

  6 months

• Estimate Progression Free Survival (PFS)

  6-12 months

Study Arms (1)

Pracinostat added to HMA

EXPERIMENTAL

Pracinostat in combination with HMA treatment (either azacitidine or decitabine) used in initial single agent treatment for that patient

Drug: pracinostat; Drug: Azacitidine; Drug: Decitabine

Interventions

pracinostat DRUG

Histone deacetylase inhibitor (HDACi) Pracinostat is to be taken before HMA administration 3 times/week (e.g., Monday, Wednesday, and Friday) for 3 weeks, followed by 1 week of rest as a 28-day cycle. Pracinostat administration will be at the clinic on Day 1 of Cycles 1 and 2 and subject will self-administer at home on all other days

Also known as: SB939

Pracinostat added to HMA

Azacitidine DRUG

All patients will receive the dose and schedule of azacitadine to which they previously failed to respond. (e.g. 75 mg/m2 via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable; 7 days of each 28 day cycle, either Days 1-7, or Days 1-5, rest on Days 6-7, and azacitadine dosing on Days 8-9)

Also known as: Vidaza

Pracinostat added to HMA

Decitabine DRUG

All patients will receive the dose and schedule of decitabine to which they previously failed to respond. Common 28 day treatment regimens include: 20 mg/m2 IV for either 5 or 10 days of each 28-day cycle, 10 mg/m2 given intravenously daily for first 10 days of each 28 day cycle, or 20 mg/m2 given subcutaneously daily for the first 5 days of each 28 day cycle. The 6-week regimen utilizes a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days repeated every 6 weeks.

Also known as: Dacogen

Pracinostat added to HMA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent
• Histologically or cytologically documented diagnosis of MDS (any French-American-British classification \[FAB\] subtype)
• Bone marrow blasts \>5% and \<30% and a peripheral white blood cell (WBC) count of \<20,000 /µL
• Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
• Group 1:
• Primary failures: Progression after their most recent HMA therapy according to IWG criteria after receiving single agent azacitidine and/or single agent decitabine, or has worsening cytopenias (increased transfusion requirement), increased BM blasts, progression to a higher FAB type, or develops additional clinically significant cytogenetic abnormalities; Secondary failures: Relapse after any initial CR, PR, HI, or development of clinically significant cytogenetic abnormalities at any time according to IWG criteria after receiving single agent azacitidine or decitabine
• Group 2:
• Failure to achieve a response (any CR, PR or HI) according to IWG criteria definition of stable disease after the most recent HMA therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine)
• Must have demonstrated tolerability to single agent HMA
• Able to start combination therapy within 3 months of the last single agent HMA dose with no other therapy for disease under study received during this interval
• Not a candidate for hematopoietic stem cell transplant within 4 months of screening
• ECOG performance status of 0, 1, or 2
• Adequate organ function as evidenced by:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN or total bilirubin of ≤2 mg/dL, whichever is higher

You may not qualify if:

• Received any of the following within the specified time frame after the last single agent HMA dose until the first administration of study medication:
• Any therapy for malignancy between the time of single agent HMA and first on-study treatment
• Hydroxyurea within 48 hours prior to first study treatment
• 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 first study treatment
• Major surgery within 28 days of study day 1
• Patients who are candidates for aggressive chemotherapy (e.g. typical AML induction therapy)
• Cardiopulmonary function criteria:
• Current unstable arrhythmia requiring treatment
• History of symptomatic congestive heart failure (New York Heart Association Class III or IV)
• History of myocardial infarction within 6 months of enrollment
• Current unstable angina
• Concomitant treatment with agents that have activity against HDAC inhibitors is not permitted
• Clinical evidence of CNS involvement
• Patients with gastrointestinal (GI) tract disease, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
• Active infection with human immunodeficiency virus or chronic hepatitis B or C

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (21)

Southern Cancer Center

Mobile, Alabama, 36608, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sutter Medical Group

Sacramento, California, 95816, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Florida Cancer Specialist South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialist North

St. Petersburg, Florida, 33705, United States

Location

Northwestern University

Chicago, Illinois, 60601, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

John Theurer Cancer Center

Hackensak, New Jersey, 07601, United States

Location

Oncology Hematology Care

Cincinati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology-Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78229, United States

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

SB939 compound; Azacitidine; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2013
• First Posted: November 25, 2013
• Study Start: December 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2016
• Last Updated: February 23, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

US (21)