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

NCT04023526 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: CULM202362019-000473-2374494550AML2001
• Study Type: interventional
• Target: 103
• Locations: 9 countries
• Sites: 56

Brief 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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (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

  Up to 3 years and 5 months

Secondary Outcomes (12)

• Percentage of Participants With CR With Partial Hematological Recovery (CRh)

  Up to 3 years and 5 months

• Percentage of Participants With CR Plus CRh

  Up to 3 years and 5 months

• Percentage of Participants With CR With Incomplete Recovery (CRi)

  Up to 3 years and 5 months

• Overall Response Rate (ORR)

  Up to 3 years and 5 months

• Percentage of Participants With CR Without MRD

  Up to 3 years and 5 months

Study Arms (2)

Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg

EXPERIMENTAL

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; Drug: Cusatuzumab

Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg

EXPERIMENTAL

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; Drug: Cusatuzumab

Interventions

Azacitidine DRUG

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

Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg; Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg

Cusatuzumab DRUG

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

Also known as: OV-1001, JNJ-74494550, ARGX-110

Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg; Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• OncoVerity, Inc.: lead
• argenx: collaborator
• Janssen Research & Development, LLC: collaborator

Study Sites (56)

St Vincents Hospital Sydney

Darlinghurst, 2010, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, 3065, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Royal Perth Hospital

Perth, 6000, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Universidade Estadual De Campinas

Campinas, 13083-878, Brazil

Location

Hospital das Clinicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

CHU d'Angers

Angers, 49933, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

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

Pessac, 33600, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059, France

Location

CHRU Tours Hôpital Bretonneau

Tours, 37000, France

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, 40138, Italy

Location

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Division of Hematology, Cardarelli Hospital

Napoli, 80131, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, 33100, Italy

Location

Chelyabinck Regional Clinical Hospital

Chelyabinsk, 454076, Russia

Location

S.P. Botkin Moscow City Clinical Hospital

Moscow, 125284, Russia

Location

City Clinical Hospital # 40

Moscow, 129301, Russia

Location

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390039, Russia

Location

St.-Petersburg Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, 193024, Russia

Location

City clinical hospital #15

Saint Petersburg, 198205, Russia

Location

Samara Region Clinical Hospital

Samara, 443095, Russia

Location

Oncologic Dispensary No.2

Sochi, 354057, Russia

Location

Komi Republic Oncology dispensary

Syktyvkar, 167904, Russia

Location

Ekaterinburg City Clinical Hospital # 7

Yekaterinburg, 620137, Russia

Location

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 08908, Spain

Location

Hosp. Univ. Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Reina Sofia

Córdoba, 14004, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. Son Espases

Palma, 7120, Spain

Location

Hosp. Clinico Univ. de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

INSELSPITAL, Universitätsspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1205, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, Switzerland

Location

Gulhane Egitim ve Arastirma Hastanesi

Ankara, 06010, Turkey (Türkiye)

Location

Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

Location

Ankara University Medical Faculty Hematology Department - Hematology

Ankara, 6100, Turkey (Türkiye)

Location

Istanbul Egitim ve Arastirma Hastanesi

Istanbul, 34098, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, 35210, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi

Samsun, 55139, Turkey (Türkiye)

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 37914483 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Clay Smith, MD Chief Medical Officer
• Organization: OncoVerity

csmith@oncoverity.com

7204981136

Study Officials

• Clayton Smith, MD

  OncoVerity, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: July 17, 2019
• Study Start: July 29, 2019
• Primary Completion: August 15, 2023
• Study Completion (Estimated): May 15, 2026
• Last Updated: August 20, 2025
• Results First Posted: July 30, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

CH (4); IL (3); IT (7); BR (2); TU (7); FR (7); ES (10); AU (5); RU (11)