Clinical Trials List
Protocol Number56022473AML2002
NCT Number(ClinicalTrials.gov Identfier)NCT02472145
2016-10-26 - 2019-07-31
Phase II/III
Terminated4
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
ICD-10C92
Myeloid leukemia
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
-
Trial Applicant
Johnson & Johnson
-
Sponsor
Janssen Research & Development, LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yu-Min Yeh Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 黃慈恩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Li-Yuan Bai Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- - - Division of Hematology & Oncology
- 李啟誠 Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- SHAN-CHI YU Division of Others -
- MING YAO Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- 劉家豪 Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
Primary Objectives
Part A
The primary objectives of Part A of the study are to assess safety and to confirm the recommended
Phase 2 dose (RP2D) of JNJ-56022473 monotherapy.
Part B
The primary objectives of Part B of the study are to assess complete response (CR) rate and overall
survival (OS) in patients with previously untreated AML who are not eligible for intense induction
chemotherapy and who are randomly assigned to receive decitabine plus JNJ-56022473 at the RP2D or
decitabine alone.
Test Drug
Talacotuzumab
Active Ingredient
Talacotuzumab
Dosage Form
Vial
Dosage
100
Endpoints
Part A
To assess safety and determine dose-limiting toxicities (DLTs)
Part B
2 Primary Endpoints (Part B)
CR rate
Overall survival (OS)
Secondary Endpoints (Part B)
EFS, defined as the time from randomization to treatment failure, relapse from CR/CRi, or death
from any cause, whichever occurs first. Treatment failure is defined as >25% absolute increase in the
bone marrow blast count from baseline to the present assessment.
ORR (CR + CRi)
Time to response, defined for subjects who achieved best response of CR or CRi as time from
randomization to achieving the best response;
Duration of response, defined for subjects who achieved best response of CR or CRi as time from
achieving CR or CRi to relapse;
Relapse-free survival (RFS) defined for subjects who achieved CR or CRi as the time from achieving
CR or CRi to disease relapse or death from any cause;
Safety profile;
Pharmacokinetics;
Immunogenicity;
MRD
Patient-reported outcomes (PROs) using the FACT-Leu and EQ 5D 5L.
Exploratory Endpoints (Part B)
Pharmacokinetic/pharmacodynamic relationships associated with biomarkers, pharmacodynamic
(PD) markers and clinical end points;
To explore biomarkers associated with clinical response
Medical resource utilization
To assess safety and determine dose-limiting toxicities (DLTs)
Part B
2 Primary Endpoints (Part B)
CR rate
Overall survival (OS)
Secondary Endpoints (Part B)
EFS, defined as the time from randomization to treatment failure, relapse from CR/CRi, or death
from any cause, whichever occurs first. Treatment failure is defined as >25% absolute increase in the
bone marrow blast count from baseline to the present assessment.
ORR (CR + CRi)
Time to response, defined for subjects who achieved best response of CR or CRi as time from
randomization to achieving the best response;
Duration of response, defined for subjects who achieved best response of CR or CRi as time from
achieving CR or CRi to relapse;
Relapse-free survival (RFS) defined for subjects who achieved CR or CRi as the time from achieving
CR or CRi to disease relapse or death from any cause;
Safety profile;
Pharmacokinetics;
Immunogenicity;
MRD
Patient-reported outcomes (PROs) using the FACT-Leu and EQ 5D 5L.
Exploratory Endpoints (Part B)
Pharmacokinetic/pharmacodynamic relationships associated with biomarkers, pharmacodynamic
(PD) markers and clinical end points;
To explore biomarkers associated with clinical response
Medical resource utilization
Inclution Criteria
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. These
criteria are applicable for both Part A and Part B of the study unless otherwise noted.
1 Criterion Modified per Amendment 1
1.1 AML according to WHO 2008 criteria fulfilling all of the following criteria:
For Part A:
Patients with AML (treatment naive or relapsed) for whom experimental therapy is
appropriate (as assessed by their treating physician);
For Part B:
Age ≥ 65 years;
De novo or secondary AML;
Previously untreated AML (except: emergency leukapheresis and/or hydroxyurea
during the screening phase to control hyperleukocytosis); Of note: treatment with
hydroxyurea has to be discontinued at least one day prior to start of study therapy;
Not eligible for standard intensive chemotherapy for induction and/or consolidation
based on documented investigator assessment of disease- and patient characteristics
as recorded in the electronic case report form (eCRF); these parameters include age,
ECOG performance status score, cytogenetic risk group,
36 and comorbidities (cardiac,
infectious, hepatic, diabetes-related, pulmonary, obesity-related, cerebrovascular
accident-related, peptic-ulcer, and others; as described by Giles 2007, Sorror 2005,
and Wheatley 2009)
Not eligible for an allogeneic hematopoietic stem cell transplantation.
2. ECOG Performance Status score of 0, 1 or 2.
3. Criterion Modified per Amendment 1
3.1 The following clinical laboratory values at screening:
Hematology:
Platelet count ≥ 10 x 109
/L (with or without transfusions)
White blood cell count (WBC) ≤ 40 x 109
/L (Note: leukopheresis or hydroxyurea is
permitted to decrease blast count but must be discontinued 1 day prior to start of
study therapy)
Hepatic:
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 times
ULN; for subjects with leukemic infiltration of the liver, AST and ALT ≤ 5 times
ULN is permitted
Total Bilirubin ≤ 1.5 times ULN
Renal:
Creatinine clearance (calculated by the Cockroft and Gault equation, Attachment 4)
≥ 40 mL/ min
4. A woman must be either:
Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for
at least 12 months;
Of childbearing potential and practicing a highly effective method of birth control
consistent with local regulations regarding the use of birth control methods for
subjects participating in clinical studies for at least 3 months: eg, established use of
oral, injected or implanted hormonal methods of contraception; placement of an
intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with
spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner
sterilization (the vasectomized partner should be the sole partner for that subject);
true abstinence (when this is in line with the preferred and usual lifestyle of the
subject)
Note: If the childbearing potential changes after start of the study (eg, woman who is
not heterosexually active becomes active, premenarchal woman experiences
menarche) a woman must begin a highly effective method of birth control, as
described above.
5. A woman of childbearing potential must have a negative serum (-human chorionic
gonadotropin [-hCG]) or urine pregnancy test at screening.
6. 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.
7. Each subject (or their legally acceptable representative) must sign an informed consent
form (ICF) indicating that he or she understands the purpose of and procedures required
for the study and are willing to participate in the study.
Each potential subject must satisfy all of the following criteria to be enrolled in the study. These
criteria are applicable for both Part A and Part B of the study unless otherwise noted.
1 Criterion Modified per Amendment 1
1.1 AML according to WHO 2008 criteria fulfilling all of the following criteria:
For Part A:
Patients with AML (treatment naive or relapsed) for whom experimental therapy is
appropriate (as assessed by their treating physician);
For Part B:
Age ≥ 65 years;
De novo or secondary AML;
Previously untreated AML (except: emergency leukapheresis and/or hydroxyurea
during the screening phase to control hyperleukocytosis); Of note: treatment with
hydroxyurea has to be discontinued at least one day prior to start of study therapy;
Not eligible for standard intensive chemotherapy for induction and/or consolidation
based on documented investigator assessment of disease- and patient characteristics
as recorded in the electronic case report form (eCRF); these parameters include age,
ECOG performance status score, cytogenetic risk group,
36 and comorbidities (cardiac,
infectious, hepatic, diabetes-related, pulmonary, obesity-related, cerebrovascular
accident-related, peptic-ulcer, and others; as described by Giles 2007, Sorror 2005,
and Wheatley 2009)
Not eligible for an allogeneic hematopoietic stem cell transplantation.
2. ECOG Performance Status score of 0, 1 or 2.
3. Criterion Modified per Amendment 1
3.1 The following clinical laboratory values at screening:
Hematology:
Platelet count ≥ 10 x 109
/L (with or without transfusions)
White blood cell count (WBC) ≤ 40 x 109
/L (Note: leukopheresis or hydroxyurea is
permitted to decrease blast count but must be discontinued 1 day prior to start of
study therapy)
Hepatic:
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 times
ULN; for subjects with leukemic infiltration of the liver, AST and ALT ≤ 5 times
ULN is permitted
Total Bilirubin ≤ 1.5 times ULN
Renal:
Creatinine clearance (calculated by the Cockroft and Gault equation, Attachment 4)
≥ 40 mL/ min
4. A woman must be either:
Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for
at least 12 months;
Of childbearing potential and practicing a highly effective method of birth control
consistent with local regulations regarding the use of birth control methods for
subjects participating in clinical studies for at least 3 months: eg, established use of
oral, injected or implanted hormonal methods of contraception; placement of an
intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with
spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner
sterilization (the vasectomized partner should be the sole partner for that subject);
true abstinence (when this is in line with the preferred and usual lifestyle of the
subject)
Note: If the childbearing potential changes after start of the study (eg, woman who is
not heterosexually active becomes active, premenarchal woman experiences
menarche) a woman must begin a highly effective method of birth control, as
described above.
5. A woman of childbearing potential must have a negative serum (-human chorionic
gonadotropin [-hCG]) or urine pregnancy test at screening.
6. 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.
7. Each subject (or their legally acceptable representative) must sign an informed consent
form (ICF) indicating that he or she understands the purpose of and procedures required
for the study and are willing to participate in the study.
Exclusion Criteria
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study. These criteria are applicable for both Part A and Part B of the study unless
otherwise noted.
1. Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARα).
2. For Part B only: Known leukemic involvement or clinical symptoms of leukemic
involvement of the central nervous system.
3. Criterion Modified per Amendment 1
3.1 Subjects who received prior treatment with a hypomethylating agent.
4. For Part A only: Subjects 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;
5. Criterion modified per Amendment 1
5.1 A history of, or current diagnosis of other malignancy; exceptions are myelodysplastic
syndrome or myelofibrosis, non-muscle invasive bladder cancer (Stage Ta), squamous
and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy
that in the opinion of the investigator, with concurrence with the sponsor's medical
monitor, is considered cured with minimal risk of recurrence or sufficiently controlled
with hormonal/anti-hormonal therapy).
6. Any active infection that is not responding to treatment.
7. Criterion Modified per Amendment 1
7.1 A history of human immunodeficiency virus (HIV) antibody positive or tests positive for
HIV if tested at screening
8. A history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV)
positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV
at Screening
9. Unstable angina or New York Heart Association class 3 or 4 congestive heart failure scale
(see Attachment 3)
10. Chronic respiratory disease requiring continuous oxygen use
11. QTcF > 470 ms, or QTcF prolongation at screening deemed clinically relevant by the
investigator
12. Criterion modified per Amendment 1
12.1 Screening left ventricular ejection fraction (LVEF) < 45%
13. Known allergies, hypersensitivity, or intolerance to JNJ-56022473 or decitabine or its
excipients16,17
14. Any condition for which, in the opinion of the investigator, participation would not be in
the best interest of the subject (eg, compromise the well-being) or that could prevent,
limit, or confound the protocol-specified assessments
15. Major surgery, (eg, requiring general anesthesia) within 4 weeks before screening, or will
not have fully recovered from surgery, or has surgery planned during the time the subject
is expected to participate in the study
Note: subjects with planned surgical procedures to be conducted under local anesthesia
may participate. In such cases, the investigator must notify the sponsor before
randomization.
Any potential subject who meets any of the following criteria will be excluded from participating
in the study. These criteria are applicable for both Part A and Part B of the study unless
otherwise noted.
1. Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARα).
2. For Part B only: Known leukemic involvement or clinical symptoms of leukemic
involvement of the central nervous system.
3. Criterion Modified per Amendment 1
3.1 Subjects who received prior treatment with a hypomethylating agent.
4. For Part A only: Subjects 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;
5. Criterion modified per Amendment 1
5.1 A history of, or current diagnosis of other malignancy; exceptions are myelodysplastic
syndrome or myelofibrosis, non-muscle invasive bladder cancer (Stage Ta), squamous
and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy
that in the opinion of the investigator, with concurrence with the sponsor's medical
monitor, is considered cured with minimal risk of recurrence or sufficiently controlled
with hormonal/anti-hormonal therapy).
6. Any active infection that is not responding to treatment.
7. Criterion Modified per Amendment 1
7.1 A history of human immunodeficiency virus (HIV) antibody positive or tests positive for
HIV if tested at screening
8. A history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV)
positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV
at Screening
9. Unstable angina or New York Heart Association class 3 or 4 congestive heart failure scale
(see Attachment 3)
10. Chronic respiratory disease requiring continuous oxygen use
11. QTcF > 470 ms, or QTcF prolongation at screening deemed clinically relevant by the
investigator
12. Criterion modified per Amendment 1
12.1 Screening left ventricular ejection fraction (LVEF) < 45%
13. Known allergies, hypersensitivity, or intolerance to JNJ-56022473 or decitabine or its
excipients16,17
14. Any condition for which, in the opinion of the investigator, participation would not be in
the best interest of the subject (eg, compromise the well-being) or that could prevent,
limit, or confound the protocol-specified assessments
15. Major surgery, (eg, requiring general anesthesia) within 4 weeks before screening, or will
not have fully recovered from surgery, or has surgery planned during the time the subject
is expected to participate in the study
Note: subjects with planned surgical procedures to be conducted under local anesthesia
may participate. In such cases, the investigator must notify the sponsor before
randomization.
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
400 participants
