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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02472145




Registration number
NCT02472145
Ethics application status
Date submitted
29/04/2015
Date registered
15/06/2015
Date last updated
19/03/2019

Titles & IDs
Public title
An Efficacy and Safety Study of Decitabine (DACOGEN) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus Decitabine (DACOGEN) Alone in Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy
Scientific title
A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients With AML Who Are Not Candidates for Intensive Chemotherapy
Secondary ID [1] 0 0
56022473AML2002
Secondary ID [2] 0 0
CR107273
Universal Trial Number (UTN)
Trial acronym
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 - Decitabine 20 mg/m^2
Treatment: Drugs - Talacotuzumab 9 mg/kg

Experimental: Decitabine plus Talacotuzumab - Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.

Active Comparator: Decitabine - Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle.


Treatment: Drugs: Decitabine 20 mg/m^2
Decitabine 20 milligram per square meter (mg/[m^2]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.

Treatment: Drugs: Talacotuzumab 9 mg/kg
Talacotuzumab 9 milligram per kilogram mg/kg on Day 8 and 22 of a 28-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment - Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/micro liter [mcL]); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [1] 0 0
Approximately up to 2.5 years
Primary outcome [2] 0 0
Part B: Overall Survival - Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [2] 0 0
Approximately up to 2.5 years
Secondary outcome [1] 0 0
Part B: Event-free Survival (EFS) Based on Investigator Assessment - EFS defined as time from randomization to treatment failure, relapse from CR/CRi, or death from any cause, whichever occurs first, per modified IWG criteria. Treatment failure: >25% absolute increase in the bone marrow blast count from baseline to present assessment (example, 20% to 46%) on bone marrow aspirate (or biopsy in case of dry tap); Relapse: Bone marrow blasts greater than equal to (>=)5%; reappearance of blasts in blood; or development of extramedullary disease; CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL);independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Endpoint reported is for Part B only as per planned analysis.
Timepoint [1] 0 0
Approximately up to 2.5 years
Secondary outcome [2] 0 0
Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate) - Percentage of participants who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/ mcL); platelet count >100 *10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [2] 0 0
Approximately up to 2.5 years
Secondary outcome [3] 0 0
Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) - Percentage of participants who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [3] 0 0
Approximately 2.5 years
Secondary outcome [4] 0 0
Part B: Time to Best Response - Time to best response is calculated as the time from the randomization date to the first documented date for the best response for participants who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [4] 0 0
Approximately 2.5 years
Secondary outcome [5] 0 0
Part B: Duration of Response (DOR) Based on Investigator Assessment - DOR defined as number of weeks from documented best response (CR or CRi) for participants who achieved CR or CRi to relapse, death due to relapse, date of censoring. As per modified IWG criteria: CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count >1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0* 10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Timepoint [5] 0 0
Approximately 2.5 years

Eligibility
Key inclusion criteria
- De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS]
or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to
WHO 2008 criteria

For Part A:

- Participants With AML: treatment naive or relapsed for whom experimental therapy is
appropriate (as assessed by their treating physician)

For Part B:

- Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have
at least one of the following: congestive heart failure or ejection fraction less than
or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter
(mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung
diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced
expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest
requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2;
prior or current malignancy that does not require concurrent treatment; unresolved
infection; 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

- Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during
the screening phase to control hyperleukocytosis but must be discontinued at least one
day prior to start of study therapy)

- Not eligible for an allogeneic hematopoietic stem cell transplantation

- ECOG Performance Status score of 0, 1 or 2

- A woman must be either: Not of childbearing potential: postmenopausal (more than [>]
45 years of age with amenorrhea for at least 12 months; If, of childbearing potential
must be practicing a highly effective method of birth control

- A woman of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening

- A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least
3 months after last study treatment
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)

- For Part B only: Known leukemic involvement or clinical symptoms of leukemic
involvement of the central nervous system

- Participants who received prior treatment with a hypomethylating agent

- For Part A only: Participants who did not recover from all clinically significant
toxicities (excluding alopecia and hematologic toxicities) of any previous surgery,
radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1

- Any uncontrolled active systemic infection that requires treatment with intravenous
(IV) antibiotics

- A history of human immunodeficiency virus (HIV) antibody positive or tests positive
for HIV if tested at screening

- Active systemic hepatitis infection requiring treatment or other clinically active
liver disease

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/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Herston
Recruitment hospital [2] 0 0
- Melbourne
Recruitment hospital [3] 0 0
- Perth
Recruitment hospital [4] 0 0
- South Woodville
Recruitment hospital [5] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- South Woodville
Recruitment postcode(s) [5] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
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United States of America
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Louisiana
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United States of America
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Michigan
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New Hampshire
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New York
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Belgium
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Antwerp
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Belgium
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Hasselt
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Belgium
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Leuven
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Liege
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Belgium
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Mons
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Turnhout
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Belgium
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Wilrijk
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France
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Grenoble Cedex 9
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France
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Lyon Cedex 08
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France
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Marseille
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Montpellier
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Nantes Cedex 2
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Paris Cedex 10
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France
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Toulouse Cedex 9
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Germany
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Dresden
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Essen
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Germany
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Frankfurt/Main
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Hamburg
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München
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Münster
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Germany
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Ulm
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Germany
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Würzburg
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Israel
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Haifa
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Israel
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Warszawa
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Nizhny Novgorod
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Ryazan
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Russian Federation
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Samara
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Spain
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Badalona, Barcelona
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Barcelona
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Madrid
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Pozuelo De Alarcon, Madrid
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Salamanca
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Sevilla
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Valencia
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Sweden
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Gothenburg
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Sweden
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Stockholm
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Sweden
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Uppsala
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Sweden
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Örebro
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Taiwan
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Chiayi
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Taiwan
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Taichung City
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Taiwan
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Tainan City
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Taiwan
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Taipei City
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Turkey
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Ankara
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Turkey
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Atakum
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Turkey
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Istanbul
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Turkey
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Izmir
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United Kingdom
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Bournemouth
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United Kingdom
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Cardiff
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United Kingdom
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of study Part A is to assess the safety of talacotuzumab (formerly
CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with
acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary
objective of study Part B are to assess complete response (CR) rate and overall survival (OS)
in participants with AML who are not eligible for intense induction chemotherapy and who are
randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.
Trial website
https://clinicaltrials.gov/show/NCT02472145
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
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

Summary results
Other publications