Clinical trial NCT04264806: 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)
Official title: A Phase 2, Randomized, Open-label 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: argenx
First posted: 2020-02-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Percentage of Participants Achieving Complete Remission (CR)
timeFrame: Up to 4 years
measure: Percentage of Participants who Achieve Transfusion Independence
timeFrame: Up to 4 years
measure: Time to Transformation of Participants to Acute Myeloid Leukemia (AML)
timeFrame: Up to 4 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Hematologic Improvement Rate
timeFrame: Up to 4 years
measure: Percentage of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 4 years
measure: Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Up to 4 years
measure: Area Under the Serum Concentration-Time Curve Within Timespan t1 to t2 (AUC[t1-t2]) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Maximum Serum Concentration (Cmax) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Minimum Serum Concentration (Cmin) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Elimination Half-Life (t1/2) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Systemic Clearance (CL) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Volume of Distribution (Vz) of Cusatuzumab
timeFrame: Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
measure: Number of Participants with Developed Antidrug Antibodies to Cusatuzumab
timeFrame: Cycle 1: Day 3 (Predose); Cycle 1: Day 17 (Predose); Cycle 2: Day 3 (Predose); Cycle 8 and 11: Day 3 (Predose) and EOT (up to 4 years)
measure: Percentage of Participants Achieving Complete Remission (CR) and Partial Remission (PR)
timeFrame: Up to 4 years
measure: Time to response
timeFrame: Up to 4 years
measure: Duration of response
timeFrame: Up to 4 years
measure: Percentage of Participants With Clinically Meaningful Improvement in Functional Assessment of Cancer Therapy - Anemia Trial Outcome Index (FACT-An TOI) Total Score
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Wollongong
country: Australia
facility: Wollongong Hospital
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner- Liga Paranaense de Combate ao Câncer
city: Florianopolis
country: Brazil
facility: Cepon - Centro De Pesquisas Oncologicas
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Instituto do cancer -COR -Hospital Mae de Deus
city: Rio De Janeiro
country: Brazil
facility: Oncoclínicas
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
city: São Paulo
country: Brazil
facility: Hospital Paulistano
city: São Paulo
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino (IDOR)
city: Angers
country: France
facility: CHU d'Angers
city: Lille
country: France
facility: Hopital Saint Vincent de Paul
city: Limoges
country: France
facility: CHU de Limoges, Hopital Dupuytren
city: Marseille
country: France
facility: Hôpital de La Conception
city: Nice
country: France
facility: CHU de Nice Hopital de l Archet
city: Paris Cedex 10
country: France
facility: Hopital Saint-Louis
city: Paris, 75
country: France
facility: Hopital Cochin APHP
city: Tours
country: France
facility: CHRU Tours Hôpital Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: CHU de Nancy_ Hôpital Brabois
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carcus Dresden
city: Freiburg Im Breisgau
country: Germany
facility: Universitätsklinik Freiburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: München
country: Germany
facility: Klinikum rechts der Isar an der Technischen Universität München
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Cona
country: Italy
facility: Azienda Ospedaliero Universitaria di Ferrara
city: Novara
country: Italy
facility: Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara
city: Orbassano
country: Italy
facility: Aou San Luigi Gonzaga
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano 'Bianchi-Melacrino-Morelli' Reggio Calabria
city: Roma
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Dzerzhinsk
country: Russian Federation
facility: Emergency Hospital of Dzerzhinsk
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg City Hospital #15
city: St-Petersburg
country: Russian Federation
facility: Clinical Research Institute of Hematology and Transfusiology
city: St. Petersburg
country: Russian Federation
facility: St.-Petersburg City Clinical Hospital nr 31
city: Syktyvkar
country: Russian Federation
facility: Oncology Dispensary of Komi Republic
city: Dammam
country: Saudi Arabia
facility: King Fahad Specialist hospital
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz Medical City
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Madrid
country: Spain
facility: Hosp. Univ. Infanta Leonor
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Palma
country: Spain
facility: Hosp. Univ. Son Espases
city: Salamanca
country: Spain
facility: Hosp. Clinico Univ. de Salamanca
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Bern
country: Switzerland
facility: INSELSPITAL, Universitätsspital Bern
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Zürich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: Ankara
country: Turkey
facility: Gulhane Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Koc Universitesi Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi
city: Leeds
country: United Kingdom
facility: St James Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: Kings College Hospital
city: Newcastle Upun Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical trials
role: STUDY_DIRECTOR
References: