A Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)

NCT04264806 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: CR1087342019-003576-4074494550MDS2001
• Study Type: interventional
• Target: N/A
• Locations: 11 countries
• Sites: 73

Brief Summary

The purpose of the study is to compare overall response rate (ORR) between treatment groups in participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) who are not eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is a composite of complete remission (CR), partial remission (PR) and marrow complete remission (mCR) as per modified International Working Group (IWG) criteria.

  Up to 4 years

Secondary Outcomes (19)

• Percentage of Participants Achieving Complete Remission (CR)

  Up to 4 years

• Percentage of Participants who Achieve Transfusion Independence

  Up to 4 years

• Time to Transformation of Participants to Acute Myeloid Leukemia (AML)

  Up to 4 years

• Progression Free Survival (PFS)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

Study Arms (2)

Azacitidine: Participants with MDS or CMML

EXPERIMENTAL

Participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) will receive azacitidine 75 milligram per meter square (mg/m\^2) body surface area (BSA) subcutaneously or Intravenously per local label on Days 1 through Day 7 of each 28-day cycle. Participants will be treated until disease progression; relapse from complete remission (CR), partial remission (PR), or marrow complete remission (mCR); transformation to acute myeloid leukemia (AML); death; or unacceptable toxicity.

Drug: Azacitidine

Azacitidine and Cusatuzumab: Participants with MDS or CMML

EXPERIMENTAL

Participants with higher-risk MDS or CMML will receive azacitidine 75 mg/m\^2 BSA subcutaneously or Intravenously per local label on Days 1 through 7 and cusatuzumab 20 mg/kg IV on Days 3 and 17 of each 28-day cycle. Participants will be treated until disease progression; relapse from CR, PR, mCR; transformation to AML; death; or unacceptable toxicity.

Drug: Azacitidine; Drug: Cusatuzumab

Interventions

Azacitidine DRUG

Participants will receive subcutaneous (SC) or intravenous (IV) injection of Azacitidine 75 mg/m\^2.

Azacitidine and Cusatuzumab: Participants with MDS or CMML; Azacitidine: Participants with MDS or CMML

Cusatuzumab DRUG

Participants will receive SC or IV injection of Cusatuzumab 20 mg/kg.

Also known as: JNJ-74494550,, ARGX-110

Azacitidine and Cusatuzumab: Participants with MDS or CMML

Eligibility Criteria

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

You may qualify if:

• Diagnosis of de novo or secondary higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) per World Health Organization (WHO) 2016 criteria
• At study entry, higher-risk MDS (intermediate, high, and very high risk MDS per Revised International Prognostic Scoring System \[IPSS R\]) OR higher-risk CMML (intermediate-2 or high risk CMML per CMML-specific Prognostic Scoring System \[CPSS-Mol\]). Participants with previous lower-risk MDS or CMML that has evolved to higher-risk MDS or CMML are eligible
• At study entry, not a candidate for Hematopoietic Stem Cell Transplantation (HSCT)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Adequate liver and renal function defined as follows: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than (\<) 3 \* upper limit of normal (ULN); Total bilirubin less than or equal to (\<=) 1.5 \* ULN, unless bilirubin rise is due to Gilbert's syndrome or of non hepatic origin; and Creatinine clearance (CrCl) greater than (\>) 30 milliliter per minute per 1.73 square meters (mL/min/1.73 m\^2) (by Modification of Diet in Renal Disease formula)

You may not qualify if:

• Received prior HSCT or any prior treatment, including hypomethylating agent (HMAs), for higher-risk MDS or CMML. Prior supportive therapies including transfusion and growth factors are acceptable
• Received prior treatment with cusatuzumab
• Presence of the breakpoint cluster region protein-Abelson murine leukemia (bcr-abl) rearrangement
• Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
• Any active systemic infection

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• argenx: collaborator

Study Sites (73)

St Vincents Hospital Sydney

Darlinghurst, 2010, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, 3065, Australia

Location

Peter MacCallum Cancer Institute

Melbourne, Australia

Location

Royal Perth Hospital

Perth, 6000, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Wollongong Hospital

Wollongong, 2500, Australia

Location

Hospital Erasto Gaertner- Liga Paranaense de Combate ao Câncer

Curitiba, 81520-060, Brazil

Location

Cepon - Centro De Pesquisas Oncologicas

Florianópolis, 88034-000, Brazil

Location

Liga Norte Riograndense Contra O Cancer

Natal, 59062-000, Brazil

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Instituto do cancer -COR -Hospital Mae de Deus

Porto Alegre, 90110-270, Brazil

Location

Oncoclínicas

Rio de Janeiro, 22250-905, Brazil

Location

Hospital de Base de São José do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

Hospital Paulistano

São Paulo, 01321-001, Brazil

Location

Instituto D'Or de Pesquisa e Ensino (IDOR)

São Paulo, 4501000, Brazil

Location

CHU d'Angers

Angers, 49933, France

Location

Hopital Saint Vincent de Paul

Lille, 59020, France

Location

CHU de Limoges, Hopital Dupuytren

Limoges, 87042, France

Location

Hôpital de La Conception

Marseille, 13005, France

Location

CHU de Nice Hopital de l Archet

Nice, 06200, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

Hopital Cochin APHP

Paris, 75674, France

Location

CHRU Tours Hôpital Bretonneau

Tours, 37000, France

Location

CHU de Nancy_ Hôpital Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Universitatsklinikum Carl Gustav Carcus Dresden

Dresden, 01307, Germany

Location

Universitätsklinik Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar an der Technischen Universität München

München, 81675, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria di Ferrara

Cona, 44124, Italy

Location

Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara

Novara, 28100, Italy

Location

Aou San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Grande Ospedale Metropolitano 'Bianchi-Melacrino-Morelli' Reggio Calabria

Reggio Calabria, 89124, Italy

Location

Fondazione Policlinico Tor Vergata

Roma, 00133, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, 606019, Russia

Location

S.P. Botkin Moscow City Clinical Hospital

Moscow, 125284, Russia

Location

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390039, Russia

Location

Saint Petersburg City Hospital #15

Saint Petersburg, 123182, Russia

Location

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, 191024, Russia

Location

St.-Petersburg City Clinical Hospital nr 31

Saint Petersburg, 197110, Russia

Location

Oncology Dispensary of Komi Republic

Syktyvkar, 167904, Russia

Location

King Fahad Specialist hospital

Dammam, 15215, Saudi Arabia

Location

King Abdulaziz Medical City

Jeddah, 21423, Saudi Arabia

Location

King Faisal Specialist Hospital & Research Center

Riyadh, 12713, Saudi Arabia

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp. Univ. Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 08908, Spain

Location

Hosp. Univ. Infanta Leonor

Madrid, 28031, Spain

Location

Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hosp. Univ. Son Espases

Palma, 7120, Spain

Location

Hosp. Clinico Univ. de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

INSELSPITAL, Universitätsspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1205, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, Switzerland

Location

Gulhane Egitim ve Arastirma Hastanesi

Ankara, 06010, Turkey (Türkiye)

Location

Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi

Ankara, 06590, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi

Istanbul, 34010, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35100, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi

Samsun, 55200, Turkey (Türkiye)

Location

St James Hospital

Leeds, LS9 7TF, United Kingdom

Location

University College London Hospitals

London, NW1 2BU, United Kingdom

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

Royal Victoria Infirmary

Newcastle Upun Tyne, NE1 4LP, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Janssen Research & Development, LLC Clinical trials

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: May 6, 2021
• Primary Completion: April 19, 2022
• Study Completion: January 28, 2025
• Last Updated: May 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (6); SA (3); GB (5); RU (8); BR (9); CH (3); FR (9); TU (7); ES (9); DE (6); IT (8)