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AzTrials

Myelodysplastic SyndromesPhase 2NCT04264806

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)

A Phase 2 study testing Azacitidine and Cusatuzumab in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Janssen Research & Development, LLC at 73 sites in 11 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine and Cusatuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
73 sitesin 11 countries
Study dates
6 May 2021to 28 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

73 sites in 11 countries.

73 sites in 11 countries

Brazil9 sites

  • Hospital Erasto Gaertner- Liga Paranaense de Combate ao Câncer

    Curitiba, 81520-060

  • Cepon - Centro De Pesquisas Oncologicas

    Florianópolis, 88034-000

  • Liga Norte Riograndense Contra O Cancer

    Natal, 59062-000

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre, 90035-903

  • Instituto do cancer -COR -Hospital Mae de Deus

    Porto Alegre, 90110-270

  • Oncoclínicas

    Rio de Janeiro, 22250-905

  • Hospital de Base de São José do Rio Preto

    São José do Rio Preto, 15090-000

  • Hospital Paulistano

    São Paulo, 01321-001

  • Instituto D'Or de Pesquisa e Ensino (IDOR)

    São Paulo, 4501000

Other trials in Brazil

France9 sites

  • CHU d'Angers

    Angers, 49933

  • Hopital Saint Vincent de Paul

    Lille, 59020

  • CHU de Limoges, Hopital Dupuytren

    Limoges, 87042

  • Hôpital de La Conception

    Marseille, 13005

  • CHU de Nice Hopital de l Archet

    Nice, 06200

  • Hopital Saint-Louis

    Paris, 75475

  • Hopital Cochin APHP

    Paris, 75674

  • CHRU Tours Hôpital Bretonneau

    Tours, 37000

  • CHU de Nancy_ Hôpital Brabois

    Vandœuvre-lès-Nancy, 54500

Other trials in France

Spain9 sites

  • Hosp. Univ. Germans Trias I Pujol

    Badalona, 08916

  • Hosp. Univ. Vall D Hebron

    Barcelona, 08035

  • Hosp. de La Santa Creu I Sant Pau

    Barcelona, 08041

  • Inst. Cat. Doncologia-H Duran I Reynals

    Barcelona, 08908

  • Hosp. Univ. Infanta Leonor

    Madrid, 28031

  • Centro Integral Oncológico Clara Campal

    Madrid, 28050

  • Hosp. Univ. Son Espases

    Palma, 7120

  • Hosp. Clinico Univ. de Salamanca

    Salamanca, 37007

  • Hosp. Virgen Del Rocio

    Seville, 41013

Other trials in Spain

Italy8 sites

  • Policlinico Sant'Orsola Malpighi

    Bologna, 40138

  • Azienda Ospedaliero Universitaria di Ferrara

    Cona, 44124

  • Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara

    Novara, 28100

  • Aou San Luigi Gonzaga

    Orbassano, 10043

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

    Reggio Calabria, 89124

  • Fondazione Policlinico Tor Vergata

    Roma, 00133

  • Policlinico Umberto I

    Roma, 00161

  • Istituto Clinico Humanitas

    Rozzano, 20089

Other trials in Italy

Russia8 sites

  • Emergency Hospital of Dzerzhinsk

    Dzerzhinsk, 606019

  • S.P. Botkin Moscow City Clinical Hospital

    Moscow, 125284

  • Nizhniy Novgorod Region Clinical Hospital

    Nizhny Novgorod, 603126

  • Ryazan Regional Clinical Hospital

    Ryazan, 390039

  • Saint Petersburg City Hospital #15

    Saint Petersburg, 123182

  • Clinical Research Institute of Hematology and Transfusiology

    Saint Petersburg, 191024

  • St.-Petersburg City Clinical Hospital nr 31

    Saint Petersburg, 197110

  • Oncology Dispensary of Komi Republic

    Syktyvkar, 167904

Other trials in Russia

Turkey (Türkiye)7 sites

  • Gulhane Egitim ve Arastirma Hastanesi

    Ankara, 06010

  • Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

    Ankara, 06200

  • Ankara Universitesi Tip Fakultesi

    Ankara, 06590

  • Koc Universitesi Hastanesi

    Istanbul, 34010

  • Ege Universitesi Tip Fakultesi

    Izmir, 35100

  • Dokuz Eylul Universitesi Tip Fakultesi

    Izmir, 35340

  • Ondokuz Mayis Universitesi Tip Fakultesi

    Samsun, 55200

Other trials in Turkey (Türkiye)

Australia6 sites

  • St Vincents Hospital Sydney

    Darlinghurst, 2010

  • St Vincents Hospital Melbourne

    Fitzroy, 3065

  • Peter MacCallum Cancer Institute

    Melbourne

  • Royal Perth Hospital

    Perth, 6000

  • Westmead Hospital

    Westmead, 2145

  • Wollongong Hospital

    Wollongong, 2500

Other trials in Australia

Germany6 sites

  • Universitatsklinikum Carl Gustav Carcus Dresden

    Dresden, 01307

  • Universitätsklinik Freiburg

    Freiburg im Breisgau, 79106

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitatsklinikum Leipzig

    Leipzig, 04103

  • Klinikum rechts der Isar an der Technischen Universität München

    München, 81675

  • Universitaetsklinikum Ulm

    Ulm, 89081

Other trials in Germany

United Kingdom5 sites

  • St James Hospital

    Leeds, LS9 7TF

  • University College London Hospitals

    London, NW1 2BU

  • Kings College Hospital

    London, SE5 9RF

  • Royal Victoria Infirmary

    Newcastle Upun Tyne, NE1 4LP

  • Churchill Hospital

    Oxford, OX3 7LE

Other trials in United Kingdom

Saudi Arabia3 sites

  • King Fahad Specialist hospital

    Dammam, 15215

  • King Abdulaziz Medical City

    Jeddah, 21423

  • King Faisal Specialist Hospital & Research Center

    Riyadh, 12713

Other trials in Saudi Arabia

Switzerland3 sites

  • INSELSPITAL, Universitätsspital Bern

    Bern, 3010

  • Hopitaux Universitaires de Geneve

    Geneva, 1205

  • UniversitaetsSpital Zuerich

    Zurich

Other trials in Switzerland

About this study

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)

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).

Read the 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.

Being tested
Azacitidine, Cusatuzumab
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

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

  • CusatuzumabDrug

    Also called JNJ-74494550,, ARGX-110

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

Study groups in NCT04264806
Study groupRoleWhat they receive
Azacitidine: Participants with MDS or CMMLExperimentalParticipants 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.
Receives: Drug: Azacitidine
Azacitidine and Cusatuzumab: Participants with MDS or CMMLExperimentalParticipants 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.
Receives: Drug: Azacitidine; Drug: Cusatuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 4 years

Secondary outcomes (19)

  1. Percentage of Participants Achieving Complete Remission (CR)

    Percentage of participants achieving CR as per IWG criteria will be reported.

    Measured: Up to 4 years

  2. 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.

    Measured: Up to 4 years

  3. 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.

    Measured: Up to 4 years

  4. 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.

    Measured: Up to 4 years

  5. Overall Survival (OS)

    OS is defined as the time from randomization to death.

    Measured: Up to 4 years

  6. 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.

    Measured: Up to 4 years

  7. 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.

    Measured: Up to 4 years

  8. Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters

    Percentage of participants with clinically significant abnormalities in laboratory parameters will be reported.

    Measured: Up to 4 years

  9. 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.

    Measured: 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])

  10. Maximum Serum Concentration (Cmax) of Cusatuzumab

    Cmax is the maximum observed serum concentration.

    Measured: 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])

  11. Minimum Serum Concentration (Cmin) of Cusatuzumab

    Cmin is the minimum observed serum concentration.

    Measured: 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])

  12. 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).

    Measured: 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])

  13. Systemic Clearance (CL) of Cusatuzumab

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

    Measured: 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])

  14. 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.

    Measured: 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])

  15. 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.

    Measured: 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)

  16. 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.

    Measured: Up to 4 years

  17. 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.

    Measured: Up to 4 years

  18. 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.

    Measured: Up to 4 years

  19. 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.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2020
  2. Study start6 May 2021 (estimated)
  3. Primary completion19 Apr 2022 (estimated)
  4. Study completion28 Jan 2025 (estimated)

Why it stopped: The cusatuzumab MDS strategy is under revision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04264806
Sponsor's protocol ID
CR108734
Other IDs
2019-003576-40, 74494550MDS2001, 2019
Status last verified
May 2022
First submitted
7 Feb 2020
Last updated
20 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine and Cusatuzumab in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Janssen Research & Development, LLC at 73 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 20 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in Brazil, France, Spain, Italy, Russia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04264806.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2022.

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