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

NCT ID: NCT04023526

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-29
• Study Completion Date: 2026-05-15

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.

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.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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

Cusatuzumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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

Cusatuzumab

Intervention Type: DRUG

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

Interventions

Azacitidine

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

Intervention Type: DRUG

Cusatuzumab

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

Intervention Type: DRUG

Other Intervention Names

OV-1001; JNJ-74494550; ARGX-110

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

argenx

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: collaborator

OncoVerity, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clayton Smith, MD

Role: STUDY_DIRECTOR

OncoVerity, Inc.

Locations

St Vincents Hospital Sydney

Darlinghurst, , Australia

St Vincents Hospital Melbourne

Fitzroy, , Australia

The Alfred Hospital

Melbourne, , Australia

Royal Perth Hospital

Perth, , Australia

Westmead Hospital

Westmead, , Australia

Universidade Estadual De Campinas

Campinas, , Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, , Brazil

CHU d'Angers

Angers, , France

CHU Grenoble

Grenoble, , France

Institut Paoli Calmettes

Marseille, , France

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

Pessac, , France

CHU Lyon Sud

Pierre-Bénite, , France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, , France

CHRU Tours Hôpital Bretonneau

Tours, , France

Rambam Medical Center

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, , Italy

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Division of Hematology, Cardarelli Hospital

Napoli, , Italy

Azienda Sanitaria Universitaria Integrata di Udine

Udine, , Italy

Chelyabinck Regional Clinical Hospital

Chelyabinsk, , Russia

S.P. Botkin Moscow City Clinical Hospital

Moscow, , Russia

City Clinical Hospital # 40

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, , Russia

Ryazan Regional Clinical Hospital

Ryazan, , Russia

St.-Petersburg Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, , Russia

City clinical hospital #15

Saint Petersburg, , Russia

Samara Region Clinical Hospital

Samara, , Russia

Oncologic Dispensary No.2

Sochi, , Russia

Komi Republic Oncology dispensary

Syktyvkar, , Russia

Ekaterinburg City Clinical Hospital # 7

Yekaterinburg, , Russia

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, Madrid, Spain

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, , Spain

Hosp. Univ. Vall D Hebron

Barcelona, , Spain

Hosp. Reina Sofia

Córdoba, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. Son Espases

Palma, , Spain

Hosp. Clinico Univ. de Salamanca

Salamanca, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Kantonsspital Aarau

Aarau, , Switzerland

INSELSPITAL, Universitätsspital Bern

Bern, , Switzerland

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Gulhane Egitim ve Arastirma Hastanesi

Ankara, , Turkey (Türkiye)

Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, , Turkey (Türkiye)

Ankara University Medical Faculty Hematology Department - Hematology

Ankara, , Turkey (Türkiye)

Istanbul Egitim ve Arastirma Hastanesi

Istanbul, , Turkey (Türkiye)

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Universitesi Tip Fakultesi

Samsun, , Turkey (Türkiye)

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

Countries

Australia; Brazil; France; Israel; Italy; Russia; Spain; Switzerland; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 37914483 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-000473-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CULM20236

Identifier Type: OTHER

Identifier Source: secondary_id

74494550AML2001

Identifier Type: OTHER

Identifier Source: secondary_id

CULM20236

Identifier Type: -

Identifier Source: org_study_id