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)

Myelodysplastic Syndromes Clinical Trial

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04264806
• Other study ID #: CR108734
• Secondary ID: 2019-003576-4074
• Status: Withdrawn
• Phase: Phase 2
• Start date: May 6, 2021
• Est. completion date: January 28, 2025

Study information

• Verified date: May 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 28, 2025
• Est. primary completion date: April 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Azacitidine
Participants will receive subcutaneous (SC) or intravenous (IV) injection of Azacitidine 75 mg/m^2.
• Cusatuzumab
Participants will receive SC or IV injection of Cusatuzumab 20 mg/kg.

Locations

Country	Name	City	State
Australia	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
Brazil	Hospital Erasto Gaertner- Liga Paranaense de Combate ao Câncer	Curitiba
Brazil	Cepon - Centro De Pesquisas Oncologicas	Florianopolis
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
France	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 Cedex 10
France	Hopital Cochin APHP	Paris, 75
France	CHRU Tours Hôpital Bretonneau	Tours
France	CHU de Nancy_ Hôpital Brabois	Vandoeuvre Les Nancy
Germany	Universitatsklinikum Carl Gustav Carcus Dresden	Dresden
Germany	Universitätsklinik Freiburg	Freiburg Im Breisgau
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Klinikum rechts der Isar an der Technischen Universität München	München
Germany	Universitaetsklinikum Ulm	Ulm
Italy	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
Russian Federation	Emergency Hospital of Dzerzhinsk	Dzerzhinsk
Russian Federation	S.P. Botkin Moscow City Clinical Hospital	Moscow
Russian Federation	Nizhniy Novgorod Region Clinical Hospital	Nizhny Novgorod
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	Saint Petersburg City Hospital #15	Saint-Petersburg
Russian Federation	Clinical Research Institute of Hematology and Transfusiology	St-Petersburg
Russian Federation	St.-Petersburg City Clinical Hospital nr 31	St. Petersburg
Russian Federation	Oncology Dispensary of Komi Republic	Syktyvkar
Saudi Arabia	King Fahad Specialist hospital	Dammam
Saudi Arabia	King Abdulaziz Medical City	Jeddah
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Barcelona
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Hosp. Univ. Infanta Leonor	Madrid
Spain	Hosp. Univ. Son Espases	Palma
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Virgen Del Rocio	Sevilla
Switzerland	INSELSPITAL, Universitätsspital Bern	Bern
Switzerland	Hopitaux Universitaires de Geneve	Geneve
Switzerland	UniversitaetsSpital Zuerich	Zürich
Turkey	Ankara Universitesi Tip Fakultesi	Ankara
Turkey	Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Gulhane Egitim ve Arastirma Hastanesi	Ankara
Turkey	Koc Universitesi Hastanesi	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Izmir
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi	Samsun
United Kingdom	St James Hospital	Leeds
United Kingdom	Kings College Hospital	London
United Kingdom	University College London Hospitals	London
United Kingdom	Royal Victoria Infirmary	Newcastle Upun Tyne
United Kingdom	Churchill Hospital	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC	argenx

Countries where clinical trial is conducted

Australia,  Brazil,  France,  Germany,  Italy,  Russian Federation,  Saudi Arabia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants Achieving Complete Remission (CR)	Percentage of participants achieving CR as per IWG criteria will be reported.	Up to 4 years
Secondary	Percentage of Participants who Achieve Transfusion Independence	Percentage of participants who achieve transfusion independence will be reported. Transfusion independence is defined as a period of greater than or equal to (>=) 56 consecutive days with no transfusion occurring between the first and last dose of study drug +30 days.	Up to 4 years
Secondary	Time to Transformation of Participants to Acute Myeloid Leukemia (AML)	Time to transformation of participants to AML will be reported. Transformation to AML is defined as >= 20% bone marrow blasts.	Up to 4 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause.	Up to 4 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death.	Up to 4 years
Secondary	Hematologic Improvement Rate	Hematologic improvement rate is defined as erythroid response (pretreatment, less than (<) 11 g/dL; hemoglobin >= 1.5 g/dL; relevant reduction of units of RBC transfusions by an absolute number of >= 4 Red blood cell (RBC) transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of <= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation; platelet response (pretreatment <100*10^9/L); absolute increase of >= 30*109/L for participants starting with >20*10^9/L platelets; increase to >20*109/L and by >= 100% for participants starting with <= 20*109/L platelets; Neutrophil response (pretreatment <1.0×10^9/L); and at least 100% increase and an absolute increase of >0.5*10^9/L.	Up to 4 years
Secondary	Percentage of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 4 years
Secondary	Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters	Percentage of participants with clinically significant abnormalities in laboratory parameters will be reported.	Up to 4 years
Secondary	Area Under the Serum Concentration-Time Curve Within Timespan t1 to t2 (AUC[t1-t2]) of Cusatuzumab	The AUC(t1-t2) is the area under the serum concentration-time curve within timespan t1 to t2.	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])
Secondary	Maximum Serum Concentration (Cmax) of Cusatuzumab	Cmax is the maximum observed serum concentration.	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])
Secondary	Minimum Serum Concentration (Cmin) of Cusatuzumab	Cmin is the minimum observed serum concentration.	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])
Secondary	Elimination Half-Life (t1/2) of Cusatuzumab	T1/2 is the time measured for the serum concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	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])
Secondary	Systemic Clearance (CL) of Cusatuzumab	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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])
Secondary	Volume of Distribution (Vz) of Cusatuzumab	The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.	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])
Secondary	Number of Participants with Developed Antidrug Antibodies to Cusatuzumab	Venous blood samples are analyzed for presence of antidrug antibodies to cusatuzumab. Participants with titer of confirmed positive samples for cusatuzumab antibodies are reported.	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)
Secondary	Percentage of Participants Achieving Complete Remission (CR) and Partial Remission (PR)	Percentage of participants achieving CR and PR as per IWG criteria will be reported.	Up to 4 years
Secondary	Time to response	Time to response for participants who achieved CR, PR and mCR responses, defined as time from randomization to achieving the first response of CR, PR, or mCR as per modified IWG criteria.	Up to 4 years
Secondary	Duration of response	Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those participants who responded.	Up to 4 years
Secondary	Percentage of Participants With Clinically Meaningful Improvement in Functional Assessment of Cancer Therapy - Anemia Trial Outcome Index (FACT-An TOI) Total Score	FACT-An is a scale in Functional Assessment of Chronic Illness Therapy Measurement System. It consists of Functional Assessment of Cancer Therapy (general version; FACT-G) and 20 questions labeled "additional concerns" that measure anemia/fatigue. FACT-G is 27-item compilation of general questions divided into 4 primary quality of life domains: physical well-being, social/family well-being, emotional wellbeing, and functional well-being. Participants will be asked to rate scale items as it applies to past 7 days, on 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). Negatively stated items will be reversed by subtracting the response from 4. After reversing the proper items, items are summed to a total to generate a score on (sub)scale. A summary Trial Outcome Index total score (FACT An TOI) will be calculated by summing physical well being, functional well being, and anemia symptoms subscales and higher is the score better is the quality of life.	Up to 4 years