A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy (CULMINATE)

August 4, 2025 updated by: OncoVerity, Inc.

A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy

The purpose of this study is to determine the efficacy of cusatuzumab in combination with azacitidine in participants with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

AML is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. As the most common form of acute leukemia, AML accounts for the largest number of annual deaths from leukemia. Over 95 percent (%) of AML blasts harvested from newly diagnosed AML participants expressed Cluster of Differentiation (CD) 70 on the cell surface. Cusatuzumab (JNJ-74494550) is a humanized monoclonal antibody of camelid origin, binding with tight affinity to human CD70. Cusatuzumab has been modified to induce enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) for therapeutic use in participants with cancer. Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity and is indicated for the treatment of adult participants with AML or intermediate 2 and high-risk myelodysplastic syndrome (MDS) with greater than 20% marrow blasts who are not eligible for hematopoietic stem cell transplantation. This study will evaluate 2 doses of cusatuzumab in combination with standard dose azacitidine in participants with AML who are not candidates for intensive chemotherapy (Part 1). Part 1 data will be reviewed by a Data Review Committee to select a preferred dose of cusatuzumab. The study will include a Screening Phase (28 days prior to randomization), a Treatment Phase, and a Follow-up Phase. The study includes evaluations like vital signs, electrocardiogram, spirometry test, serum chemistry and hematology tests.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
103

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Darlinghurst, Australia, 2010
        • St Vincents Hospital Sydney
      • Fitzroy, Australia, 3065
        • St Vincents Hospital Melbourne
      • Melbourne, Australia, 3004
        • The Alfred Hospital
      • Perth, Australia, 6000
        • Royal Perth Hospital
      • Westmead, Australia, 2145
        • Westmead Hospital
  • Brazil
      • Campinas, Brazil, 13083-878
        • Universidade Estadual de Campinas
      • Porto Alegre, Brazil, 90035-903
        • Hospital das Clinicas de Porto Alegre
  • France
      • Angers, France, 49933
        • CHU d'Angers
      • Grenoble cedex 9, France, 38043
        • Chu Grenoble
      • Marseille Cedex 9, France, 13273
        • Institut Paoli Calmettes
      • Pessac, France, 33600
        • Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
      • Pierre - Bénite Cedex, France, 69495
        • CHU Lyon Sud
      • Toulouse Cedex 9, France, 31059
        • Institut Universitaire du Cancer Toulouse Oncopole
      • Tours, France, 37000
        • CHRU Tours Hôpital Bretonneau
  • Israel
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40138
        • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
      • Brescia, Italy, 25123
        • Azienda Ospedaliera Spedali Civili di Brescia
      • Meldola, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy, 20141
        • Istituto Europeo Di Oncologia
      • Milano, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
      • Napoli, Italy, 80131
        • Division of Hematology, Cardarelli Hospital
      • Udine, Italy, 33100
        • Azienda Sanitaria Universitaria Integrata di Udine
  • Russian Federation
      • Chelyabinsk, Russian Federation, 454076
        • Chelyabinck Regional Clinical Hospital
      • Ekaterinburg, Russian Federation, 620137
        • Ekaterinburg City Clinical Hospital # 7
      • Moscow, Russian Federation, 125284
        • S.P. Botkin Moscow City Clinical Hospital
      • Moscow, Russian Federation, 129301
        • City Clinical Hospital # 40
      • Nizhniy Novgorod, Russian Federation, 603126
        • Nizhniy Novgorod Region Clinical Hospital
      • Ryazan, Russian Federation, 390039
        • Ryazan Regional Clinical Hospital
      • Saint Petersburg, Russian Federation, 198205
        • City clinical hospital #15
      • Samara, Russian Federation, 443095
        • Samara Region Clinical Hospital
      • Sochi, Russian Federation, 354057
        • Oncologic Dispensary No.2
      • St. Petersburg, Russian Federation, 193024
        • St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
      • Syktyvkar, Russian Federation, 167904
        • Komi Republic Oncology dispensary
  • Spain
      • Barcelona, Spain, 8035
        • Hosp. Univ. Vall D Hebron
      • Barcelona, Spain, 08908
        • Inst. Cat. Doncologia-H Duran I Reynals
      • Barcelona, Spain, 08025
        • Hosp. de La Santa Creu I Sant Pau
      • Cordoba, Spain, 14004
        • Hosp. Reina Sofia
      • Madrid, Spain, 28041
        • Hosp. Univ. 12 de Octubre
      • Madrid, Spain, 28034
        • Hosp. Univ. Ramon Y Cajal
      • Palma, Spain, 7120
        • Hosp. Univ. Son Espases
      • Salamanca, Spain, 37007
        • Hosp. Clinico Univ. de Salamanca
      • Valencia, Spain, 46026
        • Hosp. Univ. I Politecni La Fe
    • Madrid
      • Pozuelo De Alarcón, Madrid, Spain, 28223
        • Hosp. Quiron Madrid Pozuelo
  • Switzerland
      • Aarau, Switzerland, 5001
        • Kantonsspital Aarau
      • Bern, Switzerland, 3010
        • Inselspital, Universitätsspital Bern
      • Geneve, Switzerland, 1205
        • Hôpitaux Universitaires de Genève
      • Zürich, Switzerland
        • Universitaetsspital Zuerich
  • Turkey
      • Ankara, Turkey, 06010
        • Gulhane Egitim ve Arastirma Hastanesi
      • Ankara, Turkey, 06200
        • Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital
      • Ankara, Turkey, 6100
        • Ankara University Medical Faculty Hematology Department - Hematology
      • Istanbul, Turkey, 34098
        • Istanbul Egitim ve Arastirma Hastanesi
      • Izmir, Turkey, 35210
        • Dokuz Eylul Universitesi Tip Fakultesi
      • Samsun, Turkey, 55139
        • Ondokuz Mayis Universitesi Tip Fakultesi
      • Trabzon, Turkey, 61080
        • Karadeniz Teknik University Medical Faculty

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Acute myeloid leukemia (AML) according to World Health Organisation (WHO) 2016 criteria and fulfilling all of the following criteria that defines those who are "not candidates for intensive chemotherapy":

    1. greater than or equal to (>=)75 years of age or
    2. less than (<) 75 years of age with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2; Severe cardiac comorbidity defined as congestive heart failure or ejection fraction less than or equal to (<=) 50 percent (%); Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <=65% of expected, or forced expiratory volume in 1 second (FEV1) <=65% of expected or dyspnea at rest requiring oxygen; Moderate hepatic impairment defined according to NCI organ dysfunction classification criteria (total bilirubin >=1.5 up to 3 times upper limit of normal [ULN]); Creatinine clearance <45 milliliter per minute per 1.73 meter square (mL/ min/1.73 m^2); Comorbidity that, in the Investigator's opinion, makes the participant unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
  • De novo or secondary AML
  • Previously untreated AML (except: emergency leukapheresis, hydroxyurea, and/or 1 dose of cytarabine [example: 1-2 gram per meter square {g/m^2}] during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued >=24 hours prior to start of study drug). Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued >=24 hours prior to the start of study drug
  • Not eligible for an allogeneic hematopoietic stem cell transplantation
  • ECOG Performance Status score of 0, 1 or 2

Exclusion Criteria:

  • Acute promyelocytic leukemia
  • Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
  • Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day 3. For regular use of systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab. Treatment of adrenal insufficiency with physiologic replacement doses of corticosteroids are allowed
  • Prior treatment with a hypomethylating agent for treatment of AML or myelodysplastic syndrome (MDS)
  • Active malignancies (that is, progressing or requiring treatment in the last 24 months) other than the disease being treated under the study
  • Any active systemic infection
  • Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (that is, mannitol, an excipient of azacitidine)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg
Participants will receive azacitidine 75 milligram per meter square (mg/m^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
Drug: Azacitidine
Azacitidine SC or IV will be administered at a standard dose of 75 mg/m^2 on days 1-7 of each cycle.
Drug: Cusatuzumab
Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.
Other Names:
  • ARGX-110
  • JNJ-74494550
  • OV-1001
Experimental: Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg
Participants will receive azacitidine 75 mg/m^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
Drug: Azacitidine
Azacitidine SC or IV will be administered at a standard dose of 75 mg/m^2 on days 1-7 of each cycle.
Drug: Cusatuzumab
Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.
Other Names:
  • ARGX-110
  • JNJ-74494550
  • OV-1001

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Remission (CR)
Time Frame: Up to 3 years and 5 months
Complete remission based on European Leukemia Network (ELN) 2017 response criteria. Defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC >= 1.0 x10^9/L; platelet count >=100 x 10^9/L
Up to 3 years and 5 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With CR With Partial Hematological Recovery (CRh)
Time Frame: Up to 3 years and 5 months
CRh defined as meeting all criteria for CR except ANC >0.5x10^9/L and platelet count >50x10^9/L
Up to 3 years and 5 months
Percentage of Participants With CR Plus CRh
Time Frame: Up to 3 years and 5 months
CR plus CRh based on ELN 2017 response criteria. CR defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC >= 1.0 x10^9/L; platelet count >=100 x 10^9/L CRh defined as meeting all criteria for CR except ANC >0.5x10^9/L and platelet count >50x10^9/L
Up to 3 years and 5 months
Percentage of Participants With CR With Incomplete Recovery (CRi)
Time Frame: Up to 3 years and 5 months
CRi based on ELN 2017 response criteria. Defined as meeting all CR criteria except for residual neutropenia (ANC <1.0x10^9/L) or thrombocytopenia (platelets <100x10^9/L)
Up to 3 years and 5 months
Overall Response Rate (ORR)
Time Frame: Up to 3 years and 5 months
ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria.
Up to 3 years and 5 months
Percentage of Participants With CR Without MRD
Time Frame: Up to 3 years and 5 months
CR without minimal residual disease (MRD) defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3 by flow cytometry).
Up to 3 years and 5 months
Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
Time Frame: Up to 3 years and 5 months
Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as less than (<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).
Up to 3 years and 5 months
Time to First Response
Time Frame: Up to 3 years and 5 months
Defined as time from randomization to achieving the first response of CR, CRh, or CRi.
Up to 3 years and 5 months
Duration of First Response
Time Frame: Up to 3 years and 5 months
Defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.
Up to 3 years and 5 months
Red Blood Cell (RBC) and/or Platelets Transfusion Independence
Time Frame: Up to 3 years and 5 months
Defined as a period of at least 56 consecutive days with no transfusion of RBC and/or platelets between first dose of study drug and the last dose of study drug +30 days.
Up to 3 years and 5 months
Cusatuzumab Minimum Serum Concentration (Cmin)
Time Frame: Cycle 1 Day 3
Cmin is the minimum cusatuzumab serum concentration observed at Cycle 1 Day 3
Cycle 1 Day 3
Maximum Serum Concentration (Cmax) of Cusatuzumab
Time Frame: Cycle 1 Day 3
Cmax is the maximum cusatuzumab serum concentration observed at Cycle 1 Day 3.
Cycle 1 Day 3
Number of Participants With Anti-cusatuzumab Antibodies
Time Frame: Up to 3 years and 5 months
Number of participants exhibiting anti-drug antibodies for cusatuzumab.
Up to 3 years and 5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
OncoVerity, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Research & Development, LLC
argenx

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clayton Smith, MD, OncoVerity, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 29, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 16, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CULM20236 (Other Identifier: OncoVerity, Inc.)
  • 2019-000473-23 (EudraCT Number)
  • 74494550AML2001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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