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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04023526




Registration number
NCT04023526
Ethics application status
Date submitted
16/07/2019
Date registered
17/07/2019

Titles & IDs
Public title
A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
Scientific title
A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
Secondary ID [1] 0 0
2019-000473-23
Secondary ID [2] 0 0
CULM20236
Universal Trial Number (UTN)
Trial acronym
CULMINATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - Cusatuzumab

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.

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.


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

Treatment: Drugs: Cusatuzumab
Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Complete Remission (CR)
Timepoint [1] 0 0
Up to 3 years and 5 months
Secondary outcome [1] 0 0
Percentage of Participants With CR With Partial Hematological Recovery (CRh)
Timepoint [1] 0 0
Up to 3 years and 5 months
Secondary outcome [2] 0 0
Percentage of Participants With CR Plus CRh
Timepoint [2] 0 0
Up to 3 years and 5 months
Secondary outcome [3] 0 0
Percentage of Participants With CR With Incomplete Recovery (CRi)
Timepoint [3] 0 0
Up to 3 years and 5 months
Secondary outcome [4] 0 0
Overall Response Rate (ORR)
Timepoint [4] 0 0
Up to 3 years and 5 months
Secondary outcome [5] 0 0
Percentage of Participants With CR Without MRD
Timepoint [5] 0 0
Up to 3 years and 5 months
Secondary outcome [6] 0 0
Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
Timepoint [6] 0 0
Up to 3 years and 5 months
Secondary outcome [7] 0 0
Time to First Response
Timepoint [7] 0 0
Up to 3 years and 5 months
Secondary outcome [8] 0 0
Duration of First Response
Timepoint [8] 0 0
Up to 3 years and 5 months
Secondary outcome [9] 0 0
Red Blood Cell (RBC) and/or Platelets Transfusion Independence
Timepoint [9] 0 0
Up to 3 years and 5 months
Secondary outcome [10] 0 0
Cusatuzumab Minimum Serum Concentration (Cmin)
Timepoint [10] 0 0
Cycle 1 Day 3
Secondary outcome [11] 0 0
Maximum Serum Concentration (Cmax) of Cusatuzumab
Timepoint [11] 0 0
Cycle 1 Day 3
Secondary outcome [12] 0 0
Number of Participants With Anti-cusatuzumab Antibodies
Timepoint [12] 0 0
Up to 3 years and 5 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/08/2024
Actual
Sample size
Target
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincents Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Campinas
Country [2] 0 0
Brazil
State/province [2] 0 0
Porto Alegre
Country [3] 0 0
France
State/province [3] 0 0
Angers
Country [4] 0 0
France
State/province [4] 0 0
Grenoble cedex 9
Country [5] 0 0
France
State/province [5] 0 0
Marseille Cedex 9
Country [6] 0 0
France
State/province [6] 0 0
Pessac
Country [7] 0 0
France
State/province [7] 0 0
Pierre - Bénite Cedex
Country [8] 0 0
France
State/province [8] 0 0
Toulouse Cedex 9
Country [9] 0 0
France
State/province [9] 0 0
Tours
Country [10] 0 0
Israel
State/province [10] 0 0
Haifa
Country [11] 0 0
Israel
State/province [11] 0 0
Jerusalem
Country [12] 0 0
Israel
State/province [12] 0 0
Tel Aviv
Country [13] 0 0
Italy
State/province [13] 0 0
Bologna
Country [14] 0 0
Italy
State/province [14] 0 0
Brescia
Country [15] 0 0
Italy
State/province [15] 0 0
Meldola
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Italy
State/province [18] 0 0
Udine
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Chelyabinsk
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Ekaterinburg
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Moscow
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Nizhniy Novgorod
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Ryazan
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Saint Petersburg
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Samara
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Sochi
Country [27] 0 0
Russian Federation
State/province [27] 0 0
St. Petersburg
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Syktyvkar
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Cordoba
Country [32] 0 0
Spain
State/province [32] 0 0
Palma
Country [33] 0 0
Spain
State/province [33] 0 0
Salamanca
Country [34] 0 0
Spain
State/province [34] 0 0
Valencia
Country [35] 0 0
Switzerland
State/province [35] 0 0
Aarau
Country [36] 0 0
Switzerland
State/province [36] 0 0
Bern
Country [37] 0 0
Switzerland
State/province [37] 0 0
Geneve
Country [38] 0 0
Switzerland
State/province [38] 0 0
Zürich
Country [39] 0 0
Turkey
State/province [39] 0 0
Ankara
Country [40] 0 0
Turkey
State/province [40] 0 0
Istanbul
Country [41] 0 0
Turkey
State/province [41] 0 0
Izmir
Country [42] 0 0
Turkey
State/province [42] 0 0
Samsun
Country [43] 0 0
Turkey
State/province [43] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
OncoVerity, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
argenx
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Janssen Research & Development, LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clayton Smith, MD
Address 0 0
OncoVerity, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04023526