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

Leukemia, Myeloid, Acute Clinical Trial

— CULMINATE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04023526
• Other study ID #: CULM20236
• Secondary ID: 2019-000473-23CU
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 29, 2019
• Est. completion date: August 15, 2023

Study information

• Verified date: July 2023
• Source: OncoVerity, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 103
• Est. completion date: August 15, 2023
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
Australia	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
Brazil	Universidade Estadual De Campinas	Campinas
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
France	CHU d'Angers	Angers
France	CHU Grenoble	Grenoble cedex 9
France	Institut Paoli Calmettes	Marseille Cedex 9
France	Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie	Pessac
France	CHU Lyon Sud	Pierre - Bénite Cedex
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse Cedex 9
France	CHRU Tours Hôpital Bretonneau	Tours
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	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	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Division of Hematology, Cardarelli Hospital	Napoli
Italy	Azienda Sanitaria Universitaria Integrata di Udine	Udine
Russian Federation	Chelyabinck Regional Clinical Hospital	Chelyabinsk
Russian Federation	Ekaterinburg City Clinical Hospital # 7	Ekaterinburg
Russian Federation	City Clinical Hospital # 40	Moscow
Russian Federation	S.P. Botkin Moscow City Clinical Hospital	Moscow
Russian Federation	Nizhniy Novgorod Region Clinical Hospital	Nizhniy Novgorod
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	City clinical hospital #15	Saint Petersburg
Russian Federation	Samara Region Clinical Hospital	Samara
Russian Federation	Oncologic Dispensary No.2	Sochi
Russian Federation	St.-Petersburg Clinical Research Institute of Hematology and Transfusiology	St. Petersburg
Russian Federation	Komi Republic Oncology dispensary	Syktyvkar
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Barcelona
Spain	Hosp. Reina Sofia	Cordoba
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Univ. Son Espases	Palma
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo De Alarcon, Madrid
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	INSELSPITAL, Universitätsspital Bern	Bern
Switzerland	Hopitaux Universitaires de Geneve	Geneve
Switzerland	UniversitaetsSpital Zuerich	Zürich
Turkey	Ankara University Medical Faculty Hematology Department - Hematology	Ankara
Turkey	Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Gulhane Egitim ve Arastirma Hastanesi	Ankara
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi	Atakum
Turkey	Istanbul Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Izmir
Turkey	Karadeniz Teknik University Medical Faculty	Trabzon

Sponsors (3)

Lead Sponsor	Collaborator
OncoVerity, Inc.	argenx, Janssen Research & Development, LLC

Countries where clinical trial is conducted

Australia,  Brazil,  France,  Israel,  Italy,  Russian Federation,  Spain,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Minimum Serum Concentration (Cmin) of Cusatuzumab	Cmin is the minimum observed serum concentration.	Up to 2 years and 2 months
Secondary	Maximum Serum Concentration (Cmax) of Cusatuzumab	Cmax is the maximum observed serum concentration.	Up to 2 years and 2 months
Secondary	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