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)

NCT ID: NCT04264806

Last Updated: 2022-05-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-06
• Study Completion Date: 2025-01-28

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).

Detailed Description

Cusatuzumab (also known as JNJ-74494550 and ARGX-110) is a humanized monoclonal antibody of camelid origin that binds with high affinity to human Cluster of Differentiation 70 (CD70). Azacitidine (an Hypomethylating agent [HMA]) is approved for the treatment of higher-risk MDS in the United States (US) and the European Union (EU). Both approvals are based on data showing decreased transfusion burden, delayed progression to acute myeloid leukemia (AML), improved quality of life, and extended survival. It is hypothesized that the addition of cusatuzumab to azacitidine will result in an improvement in overall response rate (ORR) compared with azacitidine alone in participants with higher-risk MDS or CMML.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azacitidine: Participants with MDS or CMML

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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

Azacitidine and Cusatuzumab: Participants with MDS or CMML

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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

Cusatuzumab

Intervention Type: DRUG

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

Interventions

Azacitidine

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

Intervention Type: DRUG

Cusatuzumab

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

Intervention Type: DRUG

Other Intervention Names

JNJ-74494550,; ARGX-110

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

argenx

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical trials

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

St Vincents Hospital Sydney

Darlinghurst, , Australia

St Vincents Hospital Melbourne

Fitzroy, , Australia

Peter MacCallum Cancer Institute

Melbourne, , Australia

Royal Perth Hospital

Perth, , Australia

Westmead Hospital

Westmead, , Australia

Wollongong Hospital

Wollongong, , Australia

Hospital Erasto Gaertner- Liga Paranaense de Combate ao Câncer

Curitiba, , Brazil

Cepon - Centro De Pesquisas Oncologicas

Florianópolis, , Brazil

Liga Norte Riograndense Contra O Cancer

Natal, , Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, , Brazil

Instituto do cancer -COR -Hospital Mae de Deus

Porto Alegre, , Brazil

Oncoclínicas

Rio de Janeiro, , Brazil

Hospital de Base de São José do Rio Preto

São José do Rio Preto, , Brazil

Hospital Paulistano

São Paulo, , Brazil

Instituto D'Or de Pesquisa e Ensino (IDOR)

São Paulo, , Brazil

CHU d'Angers

Angers, , France

Hopital Saint Vincent de Paul

Lille, , France

CHU de Limoges, Hopital Dupuytren

Limoges, , France

Hôpital de La Conception

Marseille, , France

CHU de Nice Hopital de l Archet

Nice, , France

Hopital Saint-Louis

Paris, , France

Hopital Cochin APHP

Paris, , France

CHRU Tours Hôpital Bretonneau

Tours, , France

CHU de Nancy_ Hôpital Brabois

Vandœuvre-lès-Nancy, , France

Universitatsklinikum Carl Gustav Carcus Dresden

Dresden, , Germany

Universitätsklinik Freiburg

Freiburg im Breisgau, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Klinikum rechts der Isar an der Technischen Universität München

München, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Azienda Ospedaliero Universitaria di Ferrara

Cona, , Italy

Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara

Novara, , Italy

Aou San Luigi Gonzaga

Orbassano, , Italy

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

Reggio Calabria, , Italy

Fondazione Policlinico Tor Vergata

Roma, , Italy

Policlinico Umberto I

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, , Russia

S.P. Botkin Moscow City Clinical Hospital

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, , Russia

Ryazan Regional Clinical Hospital

Ryazan, , Russia

Saint Petersburg City Hospital #15

Saint Petersburg, , Russia

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, , Russia

St.-Petersburg City Clinical Hospital nr 31

Saint Petersburg, , Russia

Oncology Dispensary of Komi Republic

Syktyvkar, , Russia

King Fahad Specialist hospital

Dammam, , Saudi Arabia

King Abdulaziz Medical City

Jeddah, , Saudi Arabia

King Faisal Specialist Hospital & Research Center

Riyadh, , Saudi Arabia

Hosp. Univ. Germans Trias I Pujol

Badalona, , Spain

Hosp. Univ. Vall D Hebron

Barcelona, , Spain

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, , Spain

Hosp. Univ. Infanta Leonor

Madrid, , Spain

Centro Integral Oncológico Clara Campal

Madrid, , Spain

Hosp. Univ. Son Espases

Palma, , Spain

Hosp. Clinico Univ. de Salamanca

Salamanca, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

INSELSPITAL, Universitätsspital Bern

Bern, , Switzerland

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Gulhane Egitim ve Arastirma Hastanesi

Ankara, , Turkey (Türkiye)

Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, , Turkey (Türkiye)

Ankara Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

Koc Universitesi Hastanesi

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Universitesi Tip Fakultesi

Samsun, , Turkey (Türkiye)

St James Hospital

Leeds, , United Kingdom

University College London Hospitals

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

Royal Victoria Infirmary

Newcastle Upun Tyne, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Countries

Australia; Brazil; France; Germany; Italy; Russia; Saudi Arabia; Spain; Switzerland; Turkey (Türkiye); United Kingdom

Other Identifiers

2019-003576-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

74494550MDS2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108734

Identifier Type: -

Identifier Source: org_study_id