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

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: Active, not recruiting
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Azacitidine; Drug: Cusatuzumab

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: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

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
  • Pozuelo De Alarcon, Madrid, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp. Clinico Univ. de Salamanca
  • Valencia, Spain, 46026
    • Hosp. Univ. I Politecni La Fe
• 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
  • Atakum, Turkey, 55139
    • Ondokuz Mayis Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34098
    • Istanbul Egitim ve Arastirma Hastanesi
  • Izmir, Turkey, 35210
    • Dokuz Eylul Universitesi Tip Fakultesi
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: JNJ-74494550
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: JNJ-74494550

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Complete Response (CR)	Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.	Up to 3 years and 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with CR with Partial Hematological Recovery (CRh)	Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.	Up to 3 years and 5 months
Percentage of Participants with CR plus CRh	Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.	Up to 3 years and 5 months
Percentage of Participants with CR with Incomplete Recovery (CRi)	Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.	Up to 3 years and 5 months
Overall Response Rate (ORR)	ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.	Up to 3 years and 5 months
Percentage of Participants with CR without MRD	Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3; determined by central lab).	Up to 3 years and 5 months
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).	Up to 3 years and 5 months
Time to Response	Time to response, defined as time from randomization in Part 1 to achieving the first response of CR, CRh, or CRi.	Up to 3 years and 5 months
Duration of Response	Duration of response is 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) or Platelets Transfusion Independence	Transfusion independence (RBC or platelets) is defined as a period of at least 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.	Up to 3 years and 5 months
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to 3 years and 5 months
Minimum Serum Concentration (Cmin) of Cusatuzumab	Cmin is the minimum observed serum concentration.	Up to 2 years and 2 months
Maximum Serum Concentration (Cmax) of Cusatuzumab	Cmax is the maximum observed serum concentration.	Up to 2 years and 2 months
Number of Participants with Anti-cusatuzumab Antibodies	Number of participants exhibiting anti-drug antibodies for cusatuzumab alone and in combination with azacitidine will be reported.	Up to 3 years and 5 months

Collaborators and Investigators

• Sponsor: OncoVerity, Inc.
• Collaborators: Janssen Research & Development, LLC; argenx
• Investigators: Study Director: Clayton Smith, MD, OncoVerity, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Estimated): August 15, 2023
• Study Completion (Estimated): August 15, 2023

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID 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