AzTrials
AzTrials

Leukemia, Myeloid, AcutePhase 2CULMINATENCT04023526

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

A Phase 2 study testing Azacitidine and Cusatuzumab in people with Leukemia, Myeloid, Acute, run by OncoVerity, Inc. at 56 sites in 9 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
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
103 participants
Where
56 sitesin 9 countries
Study dates
29 Jul 2019to 15 May 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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":
  • greater than or equal to (>=)75 years of age or
  • 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

Who cannot join

  • 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)

Trial locations and contacts

56 sites in 9 countries.

56 sites in 9 countries

Russia11 sites

  • Chelyabinck Regional Clinical Hospital

    Chelyabinsk, 454076

  • S.P. Botkin Moscow City Clinical Hospital

    Moscow, 125284

  • City Clinical Hospital # 40

    Moscow, 129301

  • Nizhniy Novgorod Region Clinical Hospital

    Nizhny Novgorod, 603126

  • Ryazan Regional Clinical Hospital

    Ryazan, 390039

  • St.-Petersburg Clinical Research Institute of Hematology and Transfusiology

    Saint Petersburg, 193024

  • City clinical hospital #15

    Saint Petersburg, 198205

  • Samara Region Clinical Hospital

    Samara, 443095

  • Oncologic Dispensary No.2

    Sochi, 354057

  • Komi Republic Oncology dispensary

    Syktyvkar, 167904

  • Ekaterinburg City Clinical Hospital # 7

    Yekaterinburg, 620137

Other trials in Russia

Spain10 sites

  • Hosp. de La Santa Creu I Sant Pau

    Barcelona, 08025

  • Inst. Cat. Doncologia-H Duran I Reynals

    Barcelona, 08908

  • Hosp. Univ. Vall D Hebron

    Barcelona, 8035

  • Hosp. Reina Sofia

    Córdoba, 14004

  • Hosp. Univ. Ramon Y Cajal

    Madrid, 28034

  • Hosp. Univ. 12 de Octubre

    Madrid, 28041

  • Hosp. Univ. Son Espases

    Palma, 7120

  • Hosp. Quiron Madrid Pozuelo

    Pozuelo de Alarcón, Madrid, 28223

  • Hosp. Clinico Univ. de Salamanca

    Salamanca, 37007

  • Hosp. Univ. I Politecni La Fe

    Valencia, 46026

Other trials in Spain

France7 sites

  • CHU d'Angers

    Angers, 49933

  • CHU Grenoble

    Grenoble, 38043

  • Institut Paoli Calmettes

    Marseille, 13273

  • Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie

    Pessac, 33600

  • CHU Lyon Sud

    Pierre-Bénite, 69495

  • Institut Universitaire du Cancer Toulouse Oncopole

    Toulouse, 31059

  • CHRU Tours Hôpital Bretonneau

    Tours, 37000

Other trials in France

Italy7 sites

  • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

    Bologna, 40138

  • Azienda Ospedaliera Spedali Civili di Brescia

    Brescia, 25123

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, 47014

  • Istituto Europeo di Oncologia

    Milan, 20141

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • Division of Hematology, Cardarelli Hospital

    Naples, 80131

  • Azienda Sanitaria Universitaria Integrata di Udine

    Udine, 33100

Other trials in Italy

Turkey (Türkiye)7 sites

  • Gulhane Egitim ve Arastirma Hastanesi

    Ankara, 06010

  • Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

    Ankara, 06200

  • Ankara University Medical Faculty Hematology Department - Hematology

    Ankara, 6100

  • Istanbul Egitim ve Arastirma Hastanesi

    Istanbul, 34098

  • Dokuz Eylul Universitesi Tip Fakultesi

    Izmir, 35210

  • Ondokuz Mayis Universitesi Tip Fakultesi

    Samsun, 55139

  • Karadeniz Teknik University Medical Faculty

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Australia5 sites

  • St Vincents Hospital Sydney

    Darlinghurst, 2010

  • St Vincents Hospital Melbourne

    Fitzroy, 3065

  • The Alfred Hospital

    Melbourne, 3004

  • Royal Perth Hospital

    Perth, 6000

  • Westmead Hospital

    Westmead, 2145

Other trials in Australia

Switzerland4 sites

  • Kantonsspital Aarau

    Aarau, 5001

  • INSELSPITAL, Universitätsspital Bern

    Bern, 3010

  • Hopitaux Universitaires de Geneve

    Geneva, 1205

  • UniversitaetsSpital Zuerich

    Zurich

Other trials in Switzerland

Israel3 sites

  • Rambam Medical Center

    Haifa, 31096

  • Hadassah Medical Center

    Jerusalem, 9112001

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

Other trials in Israel

Brazil2 sites

  • Universidade Estadual De Campinas

    Campinas, 13083-878

  • Hospital das Clinicas de Porto Alegre

    Porto Alegre, 90035-903

Other trials in Brazil

About this study

Official title: 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.

Read the 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.

Being tested
Azacitidine, Cusatuzumab
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AzacitidineDrug

    Azacitidine SC or IV will be administered at a standard dose of 75 mg/m^2 on days 1-7 of each cycle.

  • CusatuzumabDrug

    Also called OV-1001, JNJ-74494550, ARGX-110

    Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.

Study groups in NCT04023526
Study groupRoleWhat they receive
Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kgExperimentalParticipants 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.
Receives: Drug: Azacitidine; Drug: Cusatuzumab
Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kgExperimentalParticipants 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.
Receives: Drug: Azacitidine; Drug: Cusatuzumab

What is being measured

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

  1. Percentage of Participants With Complete Remission (CR)

    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

    Measured: Up to 3 years and 5 months

Secondary outcomes (12)

  1. Percentage of Participants With CR With Partial Hematological Recovery (CRh)

    CRh defined as meeting all criteria for CR except ANC >0.5x10^9/L and platelet count >50x10^9/L

    Measured: Up to 3 years and 5 months

  2. Percentage of Participants With CR Plus CRh

    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

    Measured: Up to 3 years and 5 months

  3. Percentage of Participants With CR With Incomplete Recovery (CRi)

    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)

    Measured: Up to 3 years and 5 months

  4. Overall Response Rate (ORR)

    ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria.

    Measured: Up to 3 years and 5 months

  5. Percentage of Participants With CR Without MRD

    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).

    Measured: Up to 3 years and 5 months

  6. Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)

    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).

    Measured: Up to 3 years and 5 months

  7. Time to First Response

    Defined as time from randomization to achieving the first response of CR, CRh, or CRi.

    Measured: Up to 3 years and 5 months

  8. Duration of First Response

    Defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.

    Measured: Up to 3 years and 5 months

  9. Red Blood Cell (RBC) and/or Platelets Transfusion Independence

    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.

    Measured: Up to 3 years and 5 months

  10. Cusatuzumab Minimum Serum Concentration (Cmin)

    Cmin is the minimum cusatuzumab serum concentration observed at Cycle 1 Day 3

    Measured: Cycle 1 Day 3

  11. Maximum Serum Concentration (Cmax) of Cusatuzumab

    Cmax is the maximum cusatuzumab serum concentration observed at Cycle 1 Day 3.

    Measured: Cycle 1 Day 3

  12. Number of Participants With Anti-cusatuzumab Antibodies

    Number of participants exhibiting anti-drug antibodies for cusatuzumab.

    Measured: Up to 3 years and 5 months

Timeline

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

  1. First posted17 Jul 2019
  2. Study start29 Jul 2019
  3. Primary completion15 Aug 2023
  4. Study completion15 May 2027 (estimated)

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
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04023526
Sponsor's protocol ID
CULM20236
Other IDs
2019-000473-23, CULM20236, 74494550AML2001, 2019
Acronym
CULMINATE
Status last verified
Oct 2026
First submitted
16 Jul 2019
Last updated
30 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Pabst T, Papayannidis C, Demirkan F, Doronin V, Fogliatto LM, Guttke C, Gyan E, Hamad N, Herrera P, Hultberg A, Jacobs J, Johnson AJ, Langlois A, Ma X, Martinelli G, Arnan M, Muller R, Nottage K, Ofran Y, Ozcan M, Samoilova O, Tolbert JA, Trudel GC, Xiu L, Vey N, Wei AH. Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. Lancet Haematol. 2023 Nov;10(11):e902-e912. doi: 10.1016/S2352-3026(23)00207-7.

    PubMed 37914483

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine and Cusatuzumab in people with Leukemia, Myeloid, Acute, run by OncoVerity, Inc. at 56 sites in 9 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 7 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in Russia, Spain, France, Italy, Turkey (Türkiye) and 4 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?

Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Complete Remission (CR) (time frame: Up to 3 years and 5 months). 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 NCT04023526, which also lists 1 linked publication.

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 30 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in