Clinical Trials List
Protocol NumberCA212-016
NCT Number(ClinicalTrials.gov Identfier)NCT02305563
2017-05-09 - 2018-04-22
Phase I/II
Terminated5
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
A Phase 1/2, Open-label Randomized Study of Ulocuplumab (BMS-936564) in Combination With Low Dose Cytarabine in Subjects With Newly Diagnosed Acute Myeloid Leukemia
-
Trial Applicant
BRISTOL-MYERS SQUIBB (TAIWAN) LTD.
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Sponsor
Bristol-Myers Squibb
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Yu Lien Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
Co-Principal Investigator
- Su-Peng Yeh 未分科
Audit
None
Co-Principal Investigator
- Wei-Hong Cheng Division of Hematology & Oncology
- Yao-Yu Hsieh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yao-Yu Hsieh Division of Hematology & Oncology
- Wei-Hong Cheng Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 劉家豪 Division of General Internal Medicine
- 李啟誠 Division of General Internal Medicine
- MING YAO Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
- - - Division of General Internal Medicine
- Chien-Yuan Chen Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- Shang-Ju Wu Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- Chien-Chin Lin Division of General Internal Medicine
- Jih-Luh Tang Division of General Internal Medicine
- Wen-Chien Chou Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
Primary Objective:
In Phase 1 (escalation cohort): To assess the safety and tolerability of ulocuplumab in combination with low-dose
cytarabine (LDAC) in subjects with AML.
In Phase 2 (expansion cohort): To estimate preliminary efficacy in terms of complete remission (CR/CRi=CR+CRi)
in subjects treated at two different dose levels of ulocuplumab, 800 mg and 1000 mg, in combination with low-dose
cytarabine (LDAC).
Test Drug
Ulocuplumab (BMS-936564)
Active Ingredient
Ulocuplumab (BMS-936564)
Dosage Form
injection
Dosage
100 mg/10ml
Endpoints
Primary Endpoints:
Phase 1 (escalation cohort): DLTs in Cycle 1, and AEs, Grade 3 AEs, AEs leading to discontinuation, SAEs,
deaths and laboratory abnormalities in combination therapy during the Treatment period plus 30 days of followup will be the primary endpoints for this study. AEs will be graded according to NCI CTCAE v4.03
Phase 2 (expansion cohort): Investigator will assess best overall response. The primary endpoint will be based
on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any
subsequent ulocuplumab 800 mg for subjects in the LDAC alone arm) after all patients had an opportunity for
6 months of follow-up.
Phase 1 (escalation cohort): DLTs in Cycle 1, and AEs, Grade 3 AEs, AEs leading to discontinuation, SAEs,
deaths and laboratory abnormalities in combination therapy during the Treatment period plus 30 days of followup will be the primary endpoints for this study. AEs will be graded according to NCI CTCAE v4.03
Phase 2 (expansion cohort): Investigator will assess best overall response. The primary endpoint will be based
on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any
subsequent ulocuplumab 800 mg for subjects in the LDAC alone arm) after all patients had an opportunity for
6 months of follow-up.
Inclution Criteria
Inclusion Criteria
1. Signed Written Informed Consent
a) The signed informed consent form. Willing and able to give informed consent; this must
be obtained before performing protocol-related procedures that are not part of standard
patient care.
2. Target Population
a) Subjects who were newly diagnosed with acute myeloid leukemia based on WHO
classification (de novo or secondary) with minimum blast count of 20% (Appendix 3).
b) Investigator considers that subject is inappropriate for intensive remission induction
therapy30 and eligible for LDAC treatment if at least one of the following criteria are met:
i) Age older than 70 years
31,32
ii) ECOG performance status 3
iii) Congestive heart failure or documented cardiomyopathy with an EF 50%
iv) Creatinine ≥ 1.3 mg/dL
v) Hematopoietic Cell Transplant-comorbidity index (HCT-CI) ≥ 333,34 (Appendix 6)
vi) Any other comorbidity that the physician judges to be incompatible with conventional
intensive chemotherapy
c) Not eligible for stem cell transplantation (SCT).
d) Radiation therapy to chloromas allowed but irradiated lesion may not be used to assess
response.
e) Screening laboratory values must meet the following criteria:
i) WBC < 100,000/L
ii) Creatinine 2.0 mg/dL
iii) Aspartate aminotransferase (AST) 3 upper limit of normal (ULN)
iv) Alanine aminotransferase (ALT) 3 ULN
v) Total bilirubin 2.0 mg/dL
f) Life expectancy at least 12 weeks.
g) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3 (Appendix 4).
h) Not positive for human immunodeficiency virus (HIV).
i) No active hepatitis B or C infection. (Does not include positive serologies resulting from
passive transfer of antibodies, eg IVIG).
j) Subject Re-enrollment: This study permits the re-enrollment of a subject that has
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has
not been treated). If re-enrolled, the subject must be re-consented.
3. Age and Reproductive Status
a) Adults age 18 years of age
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours
prior to the start of study drug.
c) Women must not be breastfeeding (Even if breastfeeding is discontinued, the participation
to the study is not allowed).
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration
of treatment with study drug (s), ulocuplumab and LDAC, plus 5 half-lives of study drug
(48 days) plus 30 days (duration of ovulatory cycle) for a total of 78 days post-treatment
completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drug (s), ulocuplumab
and LDAC, plus 5 half-lives of the study drug (48 days) plus 90 days (duration of sperm
turnover) for a total of 138 days post-treatment completion.
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are
continuously not heterosexually active are also exempt from contraceptive requirements
(except in Japan), and still must undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on
the importance of pregnancy prevention and the implications of an unexpected pregnancy
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the
use of highly effective methods of contraception (Appendix 5). Highly effective methods of
contraception have a failure rate of < 1% when used consistently and correctly.
1. Signed Written Informed Consent
a) The signed informed consent form. Willing and able to give informed consent; this must
be obtained before performing protocol-related procedures that are not part of standard
patient care.
2. Target Population
a) Subjects who were newly diagnosed with acute myeloid leukemia based on WHO
classification (de novo or secondary) with minimum blast count of 20% (Appendix 3).
b) Investigator considers that subject is inappropriate for intensive remission induction
therapy30 and eligible for LDAC treatment if at least one of the following criteria are met:
i) Age older than 70 years
31,32
ii) ECOG performance status 3
iii) Congestive heart failure or documented cardiomyopathy with an EF 50%
iv) Creatinine ≥ 1.3 mg/dL
v) Hematopoietic Cell Transplant-comorbidity index (HCT-CI) ≥ 333,34 (Appendix 6)
vi) Any other comorbidity that the physician judges to be incompatible with conventional
intensive chemotherapy
c) Not eligible for stem cell transplantation (SCT).
d) Radiation therapy to chloromas allowed but irradiated lesion may not be used to assess
response.
e) Screening laboratory values must meet the following criteria:
i) WBC < 100,000/L
ii) Creatinine 2.0 mg/dL
iii) Aspartate aminotransferase (AST) 3 upper limit of normal (ULN)
iv) Alanine aminotransferase (ALT) 3 ULN
v) Total bilirubin 2.0 mg/dL
f) Life expectancy at least 12 weeks.
g) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3 (Appendix 4).
h) Not positive for human immunodeficiency virus (HIV).
i) No active hepatitis B or C infection. (Does not include positive serologies resulting from
passive transfer of antibodies, eg IVIG).
j) Subject Re-enrollment: This study permits the re-enrollment of a subject that has
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has
not been treated). If re-enrolled, the subject must be re-consented.
3. Age and Reproductive Status
a) Adults age 18 years of age
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours
prior to the start of study drug.
c) Women must not be breastfeeding (Even if breastfeeding is discontinued, the participation
to the study is not allowed).
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration
of treatment with study drug (s), ulocuplumab and LDAC, plus 5 half-lives of study drug
(48 days) plus 30 days (duration of ovulatory cycle) for a total of 78 days post-treatment
completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drug (s), ulocuplumab
and LDAC, plus 5 half-lives of the study drug (48 days) plus 90 days (duration of sperm
turnover) for a total of 138 days post-treatment completion.
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are
continuously not heterosexually active are also exempt from contraceptive requirements
(except in Japan), and still must undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on
the importance of pregnancy prevention and the implications of an unexpected pregnancy
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the
use of highly effective methods of contraception (Appendix 5). Highly effective methods of
contraception have a failure rate of < 1% when used consistently and correctly.
Exclusion Criteria
Exclusion Criteria
1. Target Disease Exceptions
a) Acute promyelocytic leukemia (FAB classification M3).
b) Current Myelodysplastic Syndrome (MDS) with blast percentage <20%
2. Previous and Concurrent Therapies
a) Prior therapy for AML, except for hydroxyurea which can be continued up to Day 21 of
Cycle 1.
b) No new investigational therapies for any reason shall be initiated within 4 weeks prior to
the first dose of ulocuplumab and also while the subject is participating in the study- Not
applicable as per Protocol Amendment 03
c) Concomitant use of other AML systemic therapy may not be used while the subject is
participating in the study while receiving ulocuplumab or LDAC as part of treatment
period.
d) Subjects taking oral or parenteral corticosteroids must be tapered off this medication prior
to the first dose of ulocuplumab and must remain discontinued from all oral and parenteral
corticosteroids while participating in the study (unless used for treatment of infusion
reactions, rash or antiemetic prophylaxis or subjects on low-dose corticosteroids [< 20 mg
prednisone or equivalent] for chronic conditions).
e) Prior hematopoietic stem cell transplant
3. Medical History and Concurrent Diseases
a) AML subjects with signs or symptoms of leukostasis/hyperleukocytosis that could be
exacerbated by ulocuplumab.
b) Unstable angina or uncontrolled congestive heart failure.
c) Any of the following on 12-lead electrocardiogram (ECG) prior to ulocuplumab
administration, confirmed by repeat:
i) PR ≥ 220 msec
ii) QRS ≥ 120 msec
iii) QT ≥ 500 msec
iv) QTc ≥ 450 msec (Fridericia correction)35
d) Any other malignancy, excluding basal or squamous cell carcinoma of the skin, in situ
melanoma, cervical carcinoma in situ, localized prostate cancer, or superficial bladder
cancer stage 0, from which the subject has not been disease-free for at least 3 years.
e) Known central nervous system involvement by malignancy.
f) Life-threatening active bleeding.
g) Known current drug or alcohol abuse.
h) Apparent active or latent tuberculosis (TB) infection (purified protein derivative [PPD] test
is not required) as indicated by any of the following: PPD recently converted to positive;
chest x-ray with evidence of infectious infiltrate; recent unexplained changes in fever/chill
patterns.
i) Respiratory disease requiring continuous supplemental oxygen.
j) Underlying medical conditions that, in the investigator’s opinion, will make the
administration of ulocuplumab hazardous or obscure the interpretation of toxicity
determination or AEs.
k) Active infection (viral, bacterial, or fungal) requiring systemic therapy within 7 days before
receiving the first dose of ulocuplumab (prophylactic antibiotic therapy is allowed);
Subjects who are judged by the investigator to be clinically well but are obligated to
complete a course of antimicrobial therapy would not be considered to have active
infection.
l) Any major surgery within 4 weeks of ulocuplumab administration.
m) Inability to tolerate venous access.
n) Any other sound medical, psychiatric and/or social reason as determined by the
investigator.
o) Presence of active graft versus host disease -Not applicable as per Protocol Amendment 03
p) Documented pulmonary disease with diffusing capacity of the lungs for carbon monoxide
(DLCO) 65% or FEV1 65%
4. Allergies and Adverse Drug Reaction
a) History of Grade 4 hypersensitivity reactions to other monoclonal antibodies, related
compounds, or excipients of ulocuplumab.
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical
(eg, infectious disease) illness.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study
subjects and that the results of the study can be used. It is imperative that subjects fully meet all
eligibility criteria
1. Target Disease Exceptions
a) Acute promyelocytic leukemia (FAB classification M3).
b) Current Myelodysplastic Syndrome (MDS) with blast percentage <20%
2. Previous and Concurrent Therapies
a) Prior therapy for AML, except for hydroxyurea which can be continued up to Day 21 of
Cycle 1.
b) No new investigational therapies for any reason shall be initiated within 4 weeks prior to
the first dose of ulocuplumab and also while the subject is participating in the study- Not
applicable as per Protocol Amendment 03
c) Concomitant use of other AML systemic therapy may not be used while the subject is
participating in the study while receiving ulocuplumab or LDAC as part of treatment
period.
d) Subjects taking oral or parenteral corticosteroids must be tapered off this medication prior
to the first dose of ulocuplumab and must remain discontinued from all oral and parenteral
corticosteroids while participating in the study (unless used for treatment of infusion
reactions, rash or antiemetic prophylaxis or subjects on low-dose corticosteroids [< 20 mg
prednisone or equivalent] for chronic conditions).
e) Prior hematopoietic stem cell transplant
3. Medical History and Concurrent Diseases
a) AML subjects with signs or symptoms of leukostasis/hyperleukocytosis that could be
exacerbated by ulocuplumab.
b) Unstable angina or uncontrolled congestive heart failure.
c) Any of the following on 12-lead electrocardiogram (ECG) prior to ulocuplumab
administration, confirmed by repeat:
i) PR ≥ 220 msec
ii) QRS ≥ 120 msec
iii) QT ≥ 500 msec
iv) QTc ≥ 450 msec (Fridericia correction)35
d) Any other malignancy, excluding basal or squamous cell carcinoma of the skin, in situ
melanoma, cervical carcinoma in situ, localized prostate cancer, or superficial bladder
cancer stage 0, from which the subject has not been disease-free for at least 3 years.
e) Known central nervous system involvement by malignancy.
f) Life-threatening active bleeding.
g) Known current drug or alcohol abuse.
h) Apparent active or latent tuberculosis (TB) infection (purified protein derivative [PPD] test
is not required) as indicated by any of the following: PPD recently converted to positive;
chest x-ray with evidence of infectious infiltrate; recent unexplained changes in fever/chill
patterns.
i) Respiratory disease requiring continuous supplemental oxygen.
j) Underlying medical conditions that, in the investigator’s opinion, will make the
administration of ulocuplumab hazardous or obscure the interpretation of toxicity
determination or AEs.
k) Active infection (viral, bacterial, or fungal) requiring systemic therapy within 7 days before
receiving the first dose of ulocuplumab (prophylactic antibiotic therapy is allowed);
Subjects who are judged by the investigator to be clinically well but are obligated to
complete a course of antimicrobial therapy would not be considered to have active
infection.
l) Any major surgery within 4 weeks of ulocuplumab administration.
m) Inability to tolerate venous access.
n) Any other sound medical, psychiatric and/or social reason as determined by the
investigator.
o) Presence of active graft versus host disease -Not applicable as per Protocol Amendment 03
p) Documented pulmonary disease with diffusing capacity of the lungs for carbon monoxide
(DLCO) 65% or FEV1 65%
4. Allergies and Adverse Drug Reaction
a) History of Grade 4 hypersensitivity reactions to other monoclonal antibodies, related
compounds, or excipients of ulocuplumab.
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical
(eg, infectious disease) illness.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study
subjects and that the results of the study can be used. It is imperative that subjects fully meet all
eligibility criteria
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
120 participants
