An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia

NCT03151408 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: PRAN-16-52
• Study Type: interventional
• Target: 406
• Locations: 15 countries
• Sites: 129

Brief Summary

This is a Phase III, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (AZA) as background therapy in patients ≥ 18 years of age with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia and cytogenetic low-risk AML, who are unfit to receive intensive remission induction chemotherapy due to age ≥ 75 years or comorbidities. Patients will be randomized in a 1:1 ratio to one of two groups: Group A (experimental group) to receive pracinostat plus AZA and Group B (control group) to receive placebo plus AZA. Randomization will be stratified by cytogenetic risk category (intermediate vs. unfavorable-risk, according to SWOG Cytogenetic Risk Category Definitions) and ECOG performance status (0-1 vs. 2). Treatments will be administered based on 28-day cycles, with pracinostat/placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and AZA administered for 7 days of each cycle. Study treatment should continue until there is documented disease progression, relapse from complete remission (CR), or non-manageable toxicity. A minimum of 6 cycles may be required to achieve a complete remission. Once permanently discontinued from study treatment, patients will enter the Long-term Follow-up phase of the study and will be followed for assessment of disease progression, if applicable, and survival every 3 months (±1 month) until death. The end of this study is defined when 390 events (deaths) have occurred and the study is unblinded for final overall survival analysis. Patients who are receiving study treatment at the end of the study may have the opportunity to continue to receive the study drugs to which they were randomized to (Post- Study Observation Period), until the Sponsor informs the Investigators of the appropriate course of action based on the study results. The Post-Study Observation Period is defined as the period starting from the end of the study for a maximum of 12 months.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  OS measures the time from randomization to death due to any cause.

  826 days

Secondary Outcomes (4)

• Morphologic Complete Remission (CR) Rate

  744 days

• Complete Remission Without Minimal Residual Disease (CRmrd) Rate

  826 days

• Cytogenetic Complete Remission (CRc) Rate

  826 days

• Transfusion Independence (TI)

  826 days

Other Outcomes (8)

• Composite Complete Remission (cCR) Rate

  744 days

• Duration of Composite Complete Remission

  744 days

• Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30)

  from baseline up to 660 days

Study Arms (2)

Pracinostat plus AZA

EXPERIMENTAL

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Drug: Pracinostat; Drug: Azacitidine

Placebo plus AZA

PLACEBO COMPARATOR

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Drug: Placebos; Drug: Azacitidine

Interventions

Pracinostat DRUG

60 mg capsule

Also known as: SB939

Pracinostat plus AZA

Placebos DRUG

capsule

Placebo plus AZA

Azacitidine DRUG

SC or IV injection

Also known as: AZA

Placebo plus AZA; Pracinostat plus AZA

Eligibility Criteria

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

You may qualify if:

• Male or female patient ≥ 18 years of age with newly diagnosed, histologically or cytologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable-risk cytogenetics
• Unable to receive intensive chemotherapy regimens at enrollment, based on one of the following:
• I. Age ≥ 75 years, or
• II. Age \< 75 years with at least 1 of the following co-morbidities:
• An ECOG performance status of 2
• Clinically significant cardiovascular disease defined as:
• i. Left ventricular ejection fraction (LVEF) ≤ 50%, measured within 3 months prior to Day 1 confirmed by ECHO/MUGA ii. Congestive heart failure requiring medical therapy iii. Chronic stable angina requiring medical therapy iv. Prior cerebrovascular accident with sequelae c. Clinically significant pulmonary disease defined as: i. Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected ii. Lung diffusing capacity for carbon monoxide (DLCO) ≤ 65% of expected Confirmed by pulmonary tests. d. Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy) e. Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, methotrexate, or similar) f. Class III obesity defined as a Body Mass Index (BMI) \> 40 kg/m2 g. Renal impairment defined as serum creatinine \> 1.3 mg/dL (\> 115 µmol/L) or creatinine clearance \<70 ml/min h. Clinically significant cognitive impairment defined as requiring medical therapy and/or assistance with activities of daily living
• % blasts in bone marrow
• Peripheral white blood cell (WBC) count 30,000/µL For cyto-reduction, hydroxyurea is allowed during screening and up to Cycle 1, Days 1-14, to reduce WBC count to \< 30,000 µL prior to Day 1. After Cycle 1, Day 14, hydroxyurea is prohibited.
• ECOG performance status ≤ 2
• Adequate organ function as evidenced by the following laboratory findings:
• Total bilirubin ≤ 2 × upper limit of normal (ULN) or \< 3 x ULN for patients with Gilbert-Meulengracht Syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN according to institutional standards or creatinine clearance ≥ 50 mL/min
• QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 ms on electrocardiogram (ECG) at Screening

You may not qualify if:

• Able to receive intensive induction chemotherapy
• AML-associated inv(16)/t(16;16)/del(16q), t(15;17) (i.e. promyelocytic leukemia) with/without secondary aberrations; t(8;21) lacking del (9q) or complex karyotypes
• Presence of an active malignant disease within the last 12 months, with the exception of adequately treated cervical cancer in-situ, non-melanoma skin cancer and superficial bladder tumors (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\]). Other malignancies may be considered after consultation with the Medical Monitor
• Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk
• Uncontrolled arrhythmias; any Class 3-4 cardiac diseases as defined by the New York Heart Association (NYHA) functional classification
• Evidence of AML central nervous system (CNS) involvement
• Previous chemotherapy for AML except for the following, which are allowed:
• Hydroxyurea for cytoreduction
• One course of hypomethylating agent therapy (i.e.; up to 7 doses of azacitidine or 3-5 days of decitabine) within 30 days prior to enrollment (Day 1)
• Use of experimental drugs ≤ 30 days prior to screening
• Received prior HDAC inhibitor therapy
• Known hypersensitivity to any components of pracinostat, azacitidine, or mannitol
• History of human immunodeficiency virus (HIV) or an active and uncontrolled infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
• Gastrointestinal (GI) tract disease that causes an inability to take oral medication, malabsorption syndrome, or 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 pracinostat and/or AZA, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study

Sponsors & Collaborators

• Helsinn Healthcare SA: lead
• Clinipace Worldwide: collaborator

Study Sites (138)

Mayo clinic hospital

Phoenix, Arizona, 85054, United States

Location

Arizona Oncology Associates, East Valley Cancer Center

Tempe, Arizona, 85284, United States

Location

University of Arizona cancer center-north campus

Tucson, Arizona, 85724, United States

Location

10666 N.Torrey Pines-Scripps Cancer Center

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093-0698, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Saint alphonsus Regional medical center-cancer care center

Boise, Idaho, 83706, United States

Location

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

Universitz of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

Location

Pontchartrain Cancer Center (Research Location)

Covington, Louisiana, 70433, United States

Location

Rcca Md Llc

Bethesda, Maryland, 20187, United States

Location

UMass Memorial medical center-university campus

Worcester, Massachusetts, 01655, United States

Location

Michigan Center of Medical Research

Farmington Hills, Michigan, 48336, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

Mayo clinic

Rochester, Minnesota, 55905, United States

Location

Mercy Research

Springfield, Missouri, 65804, United States

Location

100 Mercy Way

Joplin, Montana, 64804, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

Duke University Medical Center-2400 Pratt Street

Durham, North Carolina, 27710, United States

Location

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Mercy Clinic Oncology & Hematology

Oklahoma City, Oklahoma, 73120, United States

Location

Oklahoma cancer specialist and research institute

Tulsa, Oklahoma, 74146, United States

Location

GHS Cancer Institute

Greenville, South Carolina, 29615, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

VA North texas Health Care sytem,Dallas VA Medical Center div. Hematology Oncology

Dallas, Texas, 75216, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Emily Couric Clinical cancer center

Charlottesville, Virginia, 22908, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Thomas Reeve Chauncey

Seattle, Washington, 98108, United States

Location

Hospital italiano de Buenos Aires

Ciudad Autonoma de Buenos Aire, Buenos Aires, C1181ACH, Argentina

Location

Instituto Medico Especializado Alexander Fleming

Ciudad Autonoma de Buenos Aire, Buenos Aires, C1426ANZ, Argentina

Location

hospital Italiano la Plata

La Plata, Buenos Aires, B1900AXI, Argentina

Location

Sanatorio Britanico SA Paraguay 40, 3P

Rosario, Santa Fe Province, 2000, Argentina

Location

sanatorio Allende

Córdoba, X5000JHQ, Argentina

Location

H ospi tal Privado de Cordoba

Córdoba, X5016KEH, Argentina

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Sunshine coast university hospital

Birtinya, Queensland, 4575, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

The Northern hospital Pharmacy Department, Ground Floor

Epping, Victoria, 3076, Australia

Location

Barwon Health, University Hospital Geelong

Geelong, Victoria, 3220, Australia

Location

Austin Hospital, Clinical Trial Pharmacy

Heidelberg, Victoria, 3084, Australia

Location

Liverpool hospital

Liverpool, 2170, Australia

Location

Royal Perth Hospital

Perth, 6000, Australia

Location

Prince of Wales Hospital

Randwick, 2031, Australia

Location

Krankenhaus der Elisabethinen Linz GmbH

Linz, 4020, Austria

Location

Müllner Hauptstrabe 48

Salzburg, 5020, Austria

Location

General Hospital Hietzing

Vienna, 1130, Austria

Location

Liga Paranaense de Com bate ao Cancer - Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

Location

Ce ntro de Pesquisas Hospital Amara l Ca rvalh o

Jaú, São Paulo, 17210-080, Brazil

Location

Centro de Pesquisa Clinica do Hospital Santa Marcelina

São Paulo, São Paulo, 0827-120, Brazil

Location

Hospital de Cancer de Barretos

Barretos, 1478-400, Brazil

Location

Hospital Santa Casa de Belo Horizonte -Serviyo de Oncologia Clinica

Belo Horizonte, 30.150-221, Brazil

Location

Centro de Pesquisas Oncologicas - CEPON

Florianópolis, 88034-000, Brazil

Location

Hospital de ClÃ-nicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Institute Nacional de Cancer Jose de Alencar Gomes da Silva-INCA

Rio de Janeiro, 20231-050, Brazil

Location

Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, 09060-870, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

"Fakultni nemocnice Hradec Kralove,

Hradec Králové, 5oo 05, Czechia

Location

Fakultni nemocnice Olomuc

Olomouc, 77900, Czechia

Location

"Fakultni nemocnice Kralovske Vinohrady,

Prague, 100 34, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady,

Prague, 10034, Czechia

Location

Vseobecna fakultni nemocnice

Prague, I28 08, Czechia

Location

CHU Amiens Picardie-Site Sud-Service d'Hematologie

Amiens, 800054, France

Location

L'Hopital privé du Confluent SAS

Nantes, 44277, France

Location

CHU de Nice, Archet 1 Hospital-Hematology department

Nice, France

Location

Hospital saints Louis

Paris, 75475, France

Location

Haut-Leveque-Service d'hématologie clinique et de thérapie cellular

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Henri Becquerel

Rouen, 76028, France

Location

Klinikum St. Marien Amberg

Amberg, Bavaria, 92224, Germany

Location

Universitatsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Marien Hospital Herne-Universitätsklinikum der Ruhr-Universität Bochum

Herne, North Rhine-Westphalia, 44625, Germany

Location

Charité-Universitätsmedizin - 1. Campus Mitte

Berlin, 10117, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

SRH Wald-Klinikum Gera GmbH

Gera, 07548, Germany

Location

Staedtisches krankenhaus kiel

Kiel, 24116, Germany

Location

Universitaet Mainz

Mainz, 55131, Germany

Location

university of Pécs

Pécs, Baranya, 7624, Hungary

Location

Pecsi Egyetem I. Belgy6gyaszati Klinika

Pécs, Baranya, H-7624, Hungary

Location

St. Istvan & St. Laszlo Hospital, Deapartment of Hematology and Stem Cell Transplantation

Budapest, H-1097, Hungary

Location

University of Debrecen Clinical Center

Debrecen, H-4032, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz, Dep. Of Haematology

Kaposvár, 7400, Hungary

Location

Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz â€" Josa Andras Oktatokorhaz, Hematologiai Osztaly

Nyíregyháza, II-1065, Hungary

Location

Ospedale San Raffaele-U.O. Ematologia e TMO

Milan, Lombardy, 20132, Italy

Location

Ospedale la Maddalena, UO Oncoematologia e TMO

Palermo, PA, 90146, Italy

Location

AOU Policlinico Consorziale di Bari

Bari, 70124, Italy

Location

AOU Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera-Università Careggi

Florence, 50134, Italy

Location

Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

ospedale Vito Fazzi

Lecce, 73100, Italy

Location

Azienda Ospedaliere Antonio Cardarelli,

Naples, 80131, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

Fondazione IRCCS policlinico San Matteo Pavia

Pavia, 27100, Italy

Location

Fondazione PTV-Policlinico Tor Vergata

Roma, 00133, Italy

Location

Policlinico Universitario Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Ordine Mauriziano

Torino, 10128, Italy

Location

Wojewodzkie Wielospecjalistyczne Centrum onkologii I traumatologii

Lodz, 93-513, Poland

Location

Examen Sp. Z o.o.,

Poznan, 60-192, Poland

Location

Specjalistyc:my Szpi tal im. dra Alfreda Sokolowskiego

Wałbrzych, 58-309, Poland

Location

Uniwersytecki Szpital Kliniczny

Wroclaw, 50-556, Poland

Location

Spitalul Clinic Filantropia

Craiova, Jud.dolj, 200143, Romania

Location

Spitalul Clinic Colentina

Bucharest, 020125, Romania

Location

clinical hospital Coltea Bld

Bucharest, 030171, Romania

Location

Spitalul Universitar de Urgenta Bucuresti

Bucharest, 050098, Romania

Location

Oncological Institute "Ion Chiricuta"

Cluj-Napoca, 400015, Romania

Location

institutu Regional de Oncologie Iasi

Iași, 700483, Romania

Location

Inje university Busan Paik Hospital

Busan, 47392, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

Location

Gachon University Gil medical center, div hematology

Incheon, 21565, South Korea

Location

Seoul National University Hospital, Div.Hematology/Oncology

Seoul, 0080, South Korea

Location

Sumsung medical center

Seoul, 06351, South Korea

Location

Seoul St.Mary Hospital, div hemato-oncology

Seoul, 06591, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

Institut Català D'Oncologia (ICO)

Badalona, Barcelona, 08916, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, Extremadura, 10003, Spain

Location

Hosp.Universitario A Coruña-Hospital Teresa Herrera

A Coruña, Galicia, 15006, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Isla Baleares, 07120, Spain

Location

"Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital Univers itario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Uni vcrsitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 46013, Spain

Location

Hospital Universitario y Politecnico de La Fe

Valencia, 46026, Spain

Location

Changhua Christian Hospital

Changhua, 50006, Taiwan

Location

Hematology and Oncology, Changhwa Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospita

Taichung, 40447, Taiwan

Location

Division of Hematology, National Taiwan University Hospital

Taipei, 100, Taiwan

Location

koo-Foundation Sun Yat-Sen Cancer Center

Taipei, 112, Taiwan

Location

Royal Devon & Exeter Hospital (Wonford site)

Exeter, Devon, EX25DW, United Kingdom

Location

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, Lancashire, FY3 8NR, United Kingdom

Location

Bradford Teaching Hospitals NHS Foundation trust

Bradford, BD9 6RJ, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

SB939 compound; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; 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

Limitations and Caveats

Results of the interim analysis (OS curves crossing at about 300 days) demonstrated futility according to the planned threshold and concluded that it was unlikely to meet the primary endpoint compared to the control group at the final analysis. Based on this outcome, the decision taken was to discontinue the recruitment of patients and terminate the study.

Results Point of Contact

• Title: Francesco Scarci
• Organization: Helsinn Healthcare SA

francesco.scarci@helsinn.com

+41 (0)91 985 1946

Study Officials

• Guillermo Garcia-Manero, MD

  MD Anderson

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 12, 2017
• Study Start: June 23, 2017
• Primary Completion: August 20, 2020
• Study Completion: August 20, 2020
• Last Updated: March 10, 2022
• Results First Posted: March 10, 2022

Record last verified: 2022-02

Locations

IT (13); TW (7); AU (3); PL (4); HU (6); RO (6); KR (7); BR (10); FR (7); DE (8); ES (12); GB (5); US (30); CZ (5); AR (6)