Clinical trial NCT04023526: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: OncoVerity, Inc.
Sponsor class: INDUSTRY
Collaborators: name: argenx
name: Janssen Research & Development, LLC
First posted: 2019-07-17
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Percentage of Participants With Complete Remission (CR)
timeFrame: Up to 3 years and 5 months
Secondary outcomes:
measure: Percentage of Participants With CR With Partial Hematological Recovery (CRh)
timeFrame: Up to 3 years and 5 months
measure: Percentage of Participants With CR Plus CRh
timeFrame: Up to 3 years and 5 months
measure: Percentage of Participants With CR With Incomplete Recovery (CRi)
timeFrame: Up to 3 years and 5 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years and 5 months
measure: Percentage of Participants With CR Without MRD
timeFrame: Up to 3 years and 5 months
measure: Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
timeFrame: Up to 3 years and 5 months
measure: Time to First Response
timeFrame: Up to 3 years and 5 months
measure: Duration of First Response
timeFrame: Up to 3 years and 5 months
measure: Red Blood Cell (RBC) and/or Platelets Transfusion Independence
timeFrame: Up to 3 years and 5 months
measure: Cusatuzumab Minimum Serum Concentration (Cmin)
timeFrame: Cycle 1 Day 3
measure: Maximum Serum Concentration (Cmax) of Cusatuzumab
timeFrame: Cycle 1 Day 3
measure: Number of Participants With Anti-cusatuzumab Antibodies
timeFrame: Up to 3 years and 5 months
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Campinas
country: Brazil
facility: Universidade Estadual De Campinas
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Angers
country: France
facility: CHU d'Angers
city: Grenoble cedex 9
country: France
facility: CHU Grenoble
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Pessac
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
city: Pierre - Bénite Cedex
country: France
facility: CHU Lyon Sud
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Tours
country: France
facility: CHRU Tours Hôpital Bretonneau
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Division of Hematology, Cardarelli Hospital
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinck Regional Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: Ekaterinburg City Clinical Hospital # 7
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 40
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: City clinical hospital #15
city: Samara
country: Russian Federation
facility: Samara Region Clinical Hospital
city: Sochi
country: Russian Federation
facility: Oncologic Dispensary No.2
city: St. Petersburg
country: Russian Federation
facility: St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
city: Syktyvkar
country: Russian Federation
facility: Komi Republic Oncology dispensary
city: Pozuelo De Alarcón
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
state: Madrid
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Cordoba
country: Spain
facility: Hosp. Reina Sofia
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Palma
country: Spain
facility: Hosp. Univ. Son Espases
city: Salamanca
country: Spain
facility: Hosp. Clinico Univ. de Salamanca
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Bern
country: Switzerland
facility: INSELSPITAL, Universitätsspital Bern
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Zürich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: Ankara
country: Turkey
facility: Gulhane Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Hematology Department - Hematology
city: Istanbul
country: Turkey
facility: Istanbul Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
Study officials:
affiliation: OncoVerity, Inc.
name: Clayton Smith, MD
role: STUDY_DIRECTOR
References: