Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Myelodysplastic Syndrome Clinical Trial

— PANTHER  

Official title:

A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03268954
• Other study ID #: Pevonedistat-3001
• Secondary ID: 2017-000318-40U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 28, 2017
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine. (An event is defined as death or transformation to AML in participants with MDS or CMML, whichever occurs first, and is defined as death in participants with low-blast AML).

Description:

The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment with azacitidine. This study will look at the overall survival, event-free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine.

The study will enroll approximately 450 participants. Once enrolled, participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles:

• Pevonedistat 20 mg/m^2 and azacitidine 75 mg/m^2 combination

• Single-agent azacitidine 75 mg/m^2

All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion.

This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic, France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland, Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner.

Participants with HR MDS or CMML will have EFS follow-up study visits every month if their disease has not transformed to AML and they have not started subsequent therapy. Participants with low-blast AML will have response follow-up study visits every month until they relapse from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted every 3 months) when they have confirmed transformation to AML (for participants with HR MDS or CMML at enrollment) or experienced PD (for participants with low-blast AML at study enrollment).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 454
• Est. completion date: June 30, 2024
• Est. primary completion date: May 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML (i.e., with white blood cell [WBC] <13,000/microliter [mcL]) or low-blast acute myelogenous leukemia (AML).

2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):

• Very high (>6 points).

• High (>4.5-6 points).

• Intermediate (>3-4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.

3. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.

4. Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.

Calculation of TRM score:

• 0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >=71 years).

• + 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).

• + 0 for (platelets <50), +1 for (platelets >=50).

Exclusion Criteria:

1. Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.

2. Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.

3. Participants with AML with a WBC count >50,000/mcL. Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria.

4. Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:

• Age >75.

• Comorbidities.

• Inability to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM >=4).

• Physician decision (e.g., lack of available stem cell donor).

• The reason a participant is not eligible should be documented in the electronic case report form (eCRF).

5. Has either clinical evidence of or history of central nervous system involvement by AML.

6. Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.

7. Is diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease.

8. Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.

9. Has prothrombin time (PT) or aPTT >1.5× upper limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment.

10. Has known human immunodeficiency virus (HIV) seropositive.

11. Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.

12. Has known hepatic cirrhosis or severe preexisting hepatic impairment.

13. Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension.

14. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Azacitidine
Azacitidine intravenous or subcutaneous formulation.
• Pevonedistat
Pevonedistat intravenous infusion.

Locations

Country	Name	City	State
Australia	Icon Cancer Care Wesley	Auchenflower	Queensland
Australia	Icon Cancer Care Chermside	Chermside	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Liverpool Hospital	Liverpool
Australia	Icon Cancer Care	South Brisbane	Queensland
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	Icon Cancer Care Southport	Southport	Queensland
Belgium	Algemeen Ziekenhuis Klina	Brasschaat	Antwerpen
Belgium	AZ Sint-Jan AV	Brugge	West-Vlaanderen
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	CHU UCL Namur asbl - Site Godinne	Yvoir	Namur
Brazil	Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana
Brazil	Centro de Pesquisas Oncologicas	Florianopolis	Santa Catarina
Brazil	Liga Norte Riograndense Contra O Cancer	Natal	Rio Grande Do Norte
Brazil	Hospital de Clinicas de Porto Alegre (HCPA) - PPDS	Porto Alegre
Brazil	Universidade Federal do Rio de Janeiro - UFRJ	Rio De Janeiro
Brazil	Hospital Santa Marcelina	Sao Paulo
Brazil	Hospital Santa Marcelina	Sao Paulo
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Kaye Edmonton Clinic	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin	Tianjin
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove	Kralovehradeck Kraj
Czechia	Vseobecna Fakultni Nemocnice V Praze	Prague
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
France	CHU Angers	Angers	Maine-et-Loire
France	Hopital Cote de Nacre	Caen	Calvados
France	Centre Hospitalier Le Mans	Le Mans
France	Hopital Saint Louis	Paris
France	Hopital Saint Louis	Paris
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Marien Hospital Akademisches Lehrkrankenhaus	Dusseldorf
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitatsklinikum Tubingen	Tubingen	Baden-Wurttemberg
Greece	University Hospital of Alexandroupolis	Alexandroupolis
Greece	Athens General Hospital 'G Gennimatas'	Athens	Attiki
Greece	Attikon University General Hospital	Athens	Attiki
Greece	Laiko General Hospital of Athens	Athens
Greece	Laiko General Hospital of Athens	Athens	Attiki
Greece	University General Hospital of Ioannina	Ioannina
Greece	University General Hospital of Larissa	Larissa
Greece	University General Hospital of Patras	Patras
Greece	Georgios Papanikolaou General Hospital of Thessaloniki	Thessaloniki
Israel	Edith Wolfson Medical Center	Holon
Israel	Hadassah Medical Center PPDS -	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	ZIV Medical Center	Safed
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi	Bologna	Emilia-Romagna
Italy	ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN	Brescia	Lombardia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS Centro Di Riferimento Oncologico Della Basilicata	Rionero in Vulture
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino	Torino
Japan	Juntendo University Hospital	Bunkyo	Tokyo
Japan	Kyushu University Hospital	Fukuoka-city
Japan	Fukushima Medical University Hospital	Fukushima-shi	Hukusima
Japan	Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital	Fukuyama	Hirosima
Japan	Saitama Medical Center	Kawagoe	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe-City	Hyogo
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto-shi	Kyoto
Japan	Dokkyo Medical University Hospital	Mibu
Japan	Nagasaki University Hospital	Nagasaki
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	NTT Medical Center Tokyo	Shinagawa-ku	Tokyo
Japan	Yokohama City University Hospital	Yokohama-shi
Japan	University of Fukui Hospital	Yoshida-gun
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeongnam
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Mexico	Hematologica Alta Especialidad S.C.	Huixquilucan
Mexico	Capital Humano para Investigacion Clinica SC	Mexico
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Hematologii I Transplantologii, Budynek Centrum Medycyny N	Gdansk	Pomorskie
Poland	Swietokrzyskie Centrum Onkologii	Kielce	Swietokrzyskie
Poland	Centrum Onkologii Ziemi Lubelskiej	Lublin
Poland	Szpital Wojewodzki w Opolu	Opole
Poland	Zaklad Diagnostyki Obrazowej SOR	Opole
Poland	Instytut Hematologii i Transfuzjologii	Warszawa	Mazowieckie
Russian Federation	City Clinical Hospital # 40	Moscow
Russian Federation	North-West Federal Medical Research Center n.a. V.A. Almazov	Saint Petersburg
Russian Federation	Russian Research Institute of Hematology and Blood Transfusion	St. Petersburg
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Complejo Asistencial Universitario de Leon	Leon	Castilla Y Leon
Spain	ICO lHospitalet Hospital Duran i Reynals	LHospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Turkey	Gazi University Medical Faculty Gazi Hospital	Ankara
Turkey	Ege University Medical Faculty	Izmir
Turkey	Mersin University Medical Faculty	Mersin
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi	Samsun
Turkey	Namik Kemal University	Tekirdag
Turkey	Karadeniz Technical University Faculty of Medicine	Trabzon
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	Maidstone Hospital	Maidstone	Kent
United Kingdom	Singleton Hospital - PPDS	Swansea
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Altamonte Springs	Florida
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers (Aurora) - USOR	Aurora	Colorado
United States	Texas Oncology (Balcones) - USOR	Austin	Texas
United States	Texas Oncology (James Casey) - USOR	Austin	Texas
United States	Texas Oncology (West 38) - USOR	Austin	Texas
United States	St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Oncology and Hematology Associates of Southwest Virginia (Blacksburg) - USOR	Blacksburg	Virginia
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	SCRI Florida Cancer Specialists South	Bonita Springs	Florida
United States	Rocky Mountain Cancer Centers (Boulder) - USOR	Boulder	Colorado
United States	SCRI Florida Cancer Specialists South	Bradenton	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Brandon	Florida
United States	New Jersey Hematology Oncology Associates LLC	Brick	New Jersey
United States	Saint Alphonsus Caldwell Cancer Care Center	Caldwell	Idaho
United States	SCRI Florida Cancer Specialists South	Cape Coral	Florida
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care Inc - USOR	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - USOR	Cincinnati	Ohio
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Clearwater	Florida
United States	Fairview Hospital	Cleveland	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rocky Mountain Cancer Centers (Colorado Springs) - USOR	Colorado Springs	Colorado
United States	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc	Corona	California
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology (Medical City) - USOR	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Southern Cancer Center - USOR	Daphne	Alabama
United States	Colorado Blood Cancer Institute - PPDS	Denver	Colorado
United States	Kaiser Foundation Health Plan	Denver	Colorado
United States	Presbyterian Saint Lukes Medical Center Laboratory	Denver	Colorado
United States	Presbyterian/St. Luke's Medical Center	Denver	Colorado
United States	Quest Diagnostics, INC	Denver	Colorado
United States	Rocky Mountain Cancer Centers (Denver) - USOR	Denver	Colorado
United States	Rocky Mountain Cancer Centers (Williams) - USOR	Denver	Colorado
United States	Tennessee Oncology - DICKSON - SCRI - PPDS	Dickson	Tennessee
United States	Greenville Health System	Easley	South Carolina
United States	St. Luke's University Health Network	Easton	Pennsylvania
United States	Laboratory Corporation of America	Englewood	Colorado
United States	Oncology Hematology Care, Inc - Fairfield	Fairfield	Ohio
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Compassionate Cancer Care Medical Group Inc	Fountain Valley	California
United States	Tennessee Oncology - FRANKLIN - SCRI - PPDS	Franklin	Tennessee
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Gainesville	Florida
United States	Tennessee Oncology - GALLATIN - SCRI - PPDS	Gallatin	Tennessee
United States	Southeastern Regional Medical Center - CTCA - PPDS	Goodyear	Arizona
United States	Greenville Health System	Greenville	South Carolina
United States	Greenville Health System Cancer Institute	Greenville	South Carolina
United States	Greenville Health System	Greer	South Carolina
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Tennessee Oncology - SUMMIT - SCRI - PPDS	Hermitage	Tennessee
United States	Centerpoint Medical Center	Independence	Missouri
United States	Mayo Clinic Jacksonville - PPDS	Jacksonville	Florida
United States	HCA Midwest Health - SCRI - PPDS	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers (Lakewood) - USOR	Lakewood	Colorado
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Largo	Florida
United States	Tennessee Oncology - LEBANON - SCRI - PPDS	Lebanon	Tennessee
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Lecanto	Florida
United States	Rocky Mountain Cancer Centers (Littleton) - USOR	Littleton	Colorado
United States	Rocky Mountain Cancer Centers (Lone Tree) - USOR	Lone Tree	Colorado
United States	Rocky Mountain Cancer Centers (Longmont) - USOR	Longmont	Colorado
United States	Texas Oncology (Tyler) - USOR	Longview	Texas
United States	Oncology and Hematology Associates of Southwest Virginia (Low Moor) - USOR	Low Moor	Virginia
United States	Hillcrest Hospital Cancer Care Center	Mayfield	Ohio
United States	Baptist Health System (N Kendall) - USOR	Miami	Florida
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Southern Cancer Center - USOR	Mobile	Alabama
United States	Southern Cancer Center - USOR	Mobile	Alabama
United States	Southern Cancer Center- USOR	Mobile	Alabama
United States	Tennessee Oncology - MURFREESBORO - SCRI - PPDS	Murfreesboro	Tennessee
United States	Saint Alphonsus Medical Center	Nampa	Idaho
United States	SCRI Florida Cancer Specialists South	Naples	Florida
United States	Sarah Cannon Center for Blood Centers - SCRI - PPDS	Nashville	Tennessee
United States	Tennessee Oncolgy - BAPTIST - SCRI - PPDS	Nashville	Tennessee
United States	Tennessee Oncology - SOUTHERN HILLS - SCRI - PPDS	Nashville	Tennessee
United States	Tennessee Oncology - ST THOMAS WEST - SCRI - PPDS	Nashville	Tennessee
United States	Tennessee Oncology NASH - SCRI - PPDS	Nashville	Tennessee
United States	Tennessee Oncology SKYLINE - SCRI - PPDS	Nashville	Tennessee
United States	Texas Oncology (E Common) - USOR	New Braunfels	Texas
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	New Port Richey	Florida
United States	Weill Cornell Medical Center	New York	New York
United States	Weill Cornell Medical Center - Monitoring Location	New York	New York
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Ocala	Florida
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Orange City	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Orlando	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Rocky Mountain Cancer Centers (Parker) - USOR	Parker	Colorado
United States	SCRI Florida Cancer Specialists South	Port Charlotte	Florida
United States	Rocky Mountain Cancer Centers (Pueblo) - USOR	Pueblo	Colorado
United States	Emad Ibrahim, MD, Inc	Redlands	California
United States	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc	Riverside	California
United States	Oncology and Hematology Associates of Southwest Virginia (Roanoke) - USOR	Roanoke	Virginia
United States	Strong Memorial Hospital	Rochester	New York
United States	Texas Oncology (Round Rock) - USOR	Round Rock	Texas
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Saint Petersburg	Florida
United States	Oncology and Hematology Associates of Southwest Virginia Inc	Salem	Virginia
United States	Texas Oncology - San Antonio Medical Center - USOR	San Antonio	Texas
United States	SCRI Florida Cancer Specialists South	Sarasota	Florida
United States	SCRI Florida Cancer Specialists South	Sarasota	Florida
United States	Greenville Health System	Seneca	South Carolina
United States	Tennessee Oncology - SHELBYVILLE - SCRI - PPDS	Shelbyville	Tennessee
United States	Tennessee Oncology - SMYRNA - SCRI - PPDS	Smyrna	Tennessee
United States	Greenville Health System	Spartanburg	South Carolina
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Spring Hill	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Tampa	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Tavares	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	The Villages	Florida
United States	Rocky Mountain Cancer Centers (Thornton) - USOR	Thornton	Colorado
United States	New Jersey Hematology and Oncology	Toms River	New Jersey
United States	Arizona Oncology Associates (Orange HOPE) - USOR	Tucson	Arizona
United States	Arizona Oncology Associates (Rudasill HOPE) - USOR	Tucson	Arizona
United States	Arizona Oncology Associates (Wilmot HOPE) - USOR	Tucson	Arizona
United States	Texas Oncology (Tyler) - USOR	Tyler	Texas
United States	SCRI Florida Cancer Specialists South	Venice	Florida
United States	SCRI Florida Cancer Specialists South	Venice	Florida
United States	Medstar Research Institute	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Winter Park	Florida
United States	Oncology and Hematology Associates of Southwest Virginia	Wytheville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS)	EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization [WHO] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.	From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Overall Survival (OS)	Overall survival was defined as the time from randomization to death from any cause.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Kaplan-Meier Estimates of Six-Month Survival Rate	Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.	Up to Month 6
Secondary	Kaplan-Meier Estimates of One-Year Survival Rate	Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.	Up to Year 1
Secondary	Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30	30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.	Up to Day 30
Secondary	Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60	60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.	Up to Day 60
Secondary	Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants	Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.	From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)	CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 gram per deciliter (g/dL) hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).	From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With CR and Marrow CR	Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and >=11 g/dL Hgb, >=100*10^9/L platelets (pl), >=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment.	From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. HI: Hgb increase >=1.5 g/dL if <11 g/dL; pl increase >=30*10^9/L if baseline>20*10^9/L or increase from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of >0.5*10^9/L if baseline <1.0*10^9/L.	From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With CR and Marrow CR and PR	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%.	From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. HI: Hgb increase >=1.5 g/dL if baseline <11 g/dL; pl increase >=30*10^9/L if baseline>20*10^9/L or increases from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of >0.5*10^9/L if baseline <1.0*10^9/L.	From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With Overall Response (OR)	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. For low-blast AML-CR:morphologic leukemia-free state>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in bone marrow aspirate.	From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With Overall Response 2 (OR2)	OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:=5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,=11g/dL Hgb,=100*10^9/L pl,=1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts =50% decrease over pretreatment but still >5%;HI:Hgb increase(inc) =1.5g/dL if baseline(BL)<11 g/dL;pl inc=30*10^9/L if BL>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of >0.5*10^9/L if BL<100*10^9/L.For low-blast AML-CR:morphologic leukemia-free state >1.0*10^9 neutrophils,=100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl<100*10^9/L;PR:all CR hematological values but =50% decrease in BM aspirate.Number of responders determined by independent review committee(IRC) assessment.	From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Duration of Complete Remission (CR)	Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).	From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)	Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).	From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Duration of Overall Response (OR)	Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still >5%. For low-blast AML-CR: morphologic leukemia-free state >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in % of blasts in bone marrow aspirate.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Duration of Overall Response 2 (OR2)	Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb, >=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment, still >5%; HI:Hgb inc >=1.5 g/dL if baseline <11 g/dL; pl inc>=30*10^9/L if baseline>20*10^9/L or inc from<20*10^9/L to>20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L;PR:all CR hematological values but>=50% decrease in bone marrow aspirate.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence	A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence	Duration of RBC and platelet transfusion independence was defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or platelet transfusion-independent period and the first RBC and/or platelet transfusion after the start of the transfusion-independent period, which occurs >= 8 weeks later.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)	Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%; For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9/L neutrophils, pl>=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.	From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With Hematologic Improvement (HI)	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase >=1.5 g/dL if baseline <11 g/dL; pl increase >=30*10^9/L if baseline >20*10^9/L or increase from <20*10^9/L to >20*10^9/L by at least 100%; neutrophil increase by 100% and absolute increase of >0.5*10^9/L if baseline <1.0*10^9/L.	From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML	Inpatient hospital admission data was collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurred first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.	From randomization until transformation to AML or until initiation of subsequent therapy till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death	Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with<5% blasts:>=50% inc >5% blasts, with 5%-9% blasts:>=50% inc>10% blasts, with 10%-19% blasts:>=50% inc >20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by>=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of >=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.>=1.5 g/dL/transfusion dependence. In AML,PD:>50% inc in bone marrow blasts to >30% blasts,>50% inc in circulating blasts to>30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.	From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30	The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Plasma Concentration of Pevonedistat		Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose (Cycle length= 28 days)
Secondary	Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%. For low-blast AML-CR: morphologic leukemia-free state, >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl<100*10^9/L; PR: all CR hematological values but>=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.	From randomization until CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group	Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was defined, according to World Health Organization (WHO) Classification as a participant having >20% blasts in the blood or marrow and increase of blast count by 50%. Event was defined as death in participants with low-blast AML.	From randomization until transformation to AML if eligible or death till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group	OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.	From randomization until death till data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary	Number of Participants With Overall Response by Cycle 6	Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR and PR for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11g/dL hemoglobin (Hgb),>=100*10^9/L platelet (pl),>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. For low-blast AML-CR:morphologic leukemia-free state,>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia <1.0*10^9/L/thrombocytopenia (pl<100*10^9/L); PR:all CR hematological values but>=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.	Up to Cycle 6 (up to approximately Day 168)

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