Clinical Trials List
Protocol NumberSGN33A-005
NCT Number(ClinicalTrials.gov Identfier)NCT02785900
2016-09-08 - 2019-10-31
Phase III
Terminated4
ICD-10C92
Myeloid leukemia
A randomized, double-blind phase 3 study of vadastuximab talirine (SGN-CD33A) versus placebo in combination with azacitidine or decitabine in the treatment of older patients with newly diagnosed acute myeloid leukemia (AML)
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Seattle Genetics, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
6 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- - - 無
- Chien-Yuan Chen 無
- Tai-Chung Huang 無
- CHENG-HONG TSAI 無
- Jih-Luh Tang 無
- 林建廷 無
- 劉家豪 無
- MING YAO 無
- Shang-Ju Wu 無
- Huai-Hsuan Huang 無
- 李啟誠 無
- HSIN-AN HOU 無
- Chien-Chin Lin 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
Primary
● To compare overall survival (OS) between treatment arms
Secondary
● To compare the composite complete remission (CRc) rate (complete remission [CR] and morphologic CR
with incomplete hematologic recovery [CRi]) between treatment arms
● To compare event-free survival (EFS) between treatment arms
● To evaluate leukemia-free survival (LFS) in the 2 treatment arms
● To evaluate the duration of remission in the 2 treatment arms
● To evaluate the safety profiles in the 2 treatment arms
● To evaluate the time to response in the 2 treatment arms
● To evaluate the 30- and 60-day mortality rates in the 2 treatment arms
● To evaluate minimal residual disease (MRD) status
Test Drug
Vadastuximab Talirine
Active Ingredient
Vadastuximab Talirine;
Dosage Form
vial
Dosage
5
Endpoints
Efficacy Assessments
Anti-leukemic activity will be assessed by routine laboratory tests and bone marrow examinations. Response
will be determined according to a modification of the response categorization in the Revised Recommendations
of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes,
and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (Cheson 2003).
Safety Assessments
Safety assessments will include the surveillance and recording of adverse events (AEs), physical examination
findings, and laboratory tests.
Quality of Life Assessments
Patient-reported outcome (PRO) assessments will be used to obtain quality of life information at
protocol-specified timepoints. Two validated tools will be used: the EORTC Quality of Life Questionnaire,
QLQ-C30, and the EuroQol 5-dimensions (EQ-5D).
Pharmacokinetic, ATA, and Biomarker Assessments
Validated enzyme-linked immunosorbent assays (ELISA) and liquid chromatography-tandem mass
spectrometry (LC-MS/MS) assays will be used to measure vadastuximab talirine and its associated drug,
SGD-1882, respectively. A qualified electrochemiluminescence assay will be used to measure concentrations
of ATA in serum. Biomarker assessments may include central assessment of CD33 expression, profiling for
somatic mutations or alterations in genes or RNAs commonly altered in hematologic malignancies, and other
genes or RNAs potentially associated with disease relapse or resistance to vadastuximab talirine. MRD will be
measured. Additional assessments may include measurement of soluble factors such as sCD33 that may be
associated with clinical outcome.
Anti-leukemic activity will be assessed by routine laboratory tests and bone marrow examinations. Response
will be determined according to a modification of the response categorization in the Revised Recommendations
of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes,
and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (Cheson 2003).
Safety Assessments
Safety assessments will include the surveillance and recording of adverse events (AEs), physical examination
findings, and laboratory tests.
Quality of Life Assessments
Patient-reported outcome (PRO) assessments will be used to obtain quality of life information at
protocol-specified timepoints. Two validated tools will be used: the EORTC Quality of Life Questionnaire,
QLQ-C30, and the EuroQol 5-dimensions (EQ-5D).
Pharmacokinetic, ATA, and Biomarker Assessments
Validated enzyme-linked immunosorbent assays (ELISA) and liquid chromatography-tandem mass
spectrometry (LC-MS/MS) assays will be used to measure vadastuximab talirine and its associated drug,
SGD-1882, respectively. A qualified electrochemiluminescence assay will be used to measure concentrations
of ATA in serum. Biomarker assessments may include central assessment of CD33 expression, profiling for
somatic mutations or alterations in genes or RNAs commonly altered in hematologic malignancies, and other
genes or RNAs potentially associated with disease relapse or resistance to vadastuximab talirine. MRD will be
measured. Additional assessments may include measurement of soluble factors such as sCD33 that may be
associated with clinical outcome.
Inclution Criteria
1. Patients with newly diagnosed, previously untreated, cytologically or histologically confirmed de novo or
secondary AML according to WHO classification (except for acute promyelocytic leukemia [APL]).
2. Age ≥65 years.
3. Life expectancy of at least 12 weeks.
4. Patient is eligible for therapy with either decitabine or azacitidine.
5. ECOG performance status ≤2 .
6. The following baseline laboratory data:
● White blood cell (WBC) count <30,000/µL; use of hydroxyurea to control WBC is acceptable.
● Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert’s disease,
or direct bilirubin ≤ 2 x ULN if total bilirubin is abnormal.
● Serum creatinine ≤2.5 x ULN and estimated creatinine clearance ≥30 mL/min.
● Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.
7. Males who have partners of childbearing potential must agree to use 2 effective contraception methods
during the study and for 6 months following the last dose of study drug.
8. Patients must provide written informed consent.
secondary AML according to WHO classification (except for acute promyelocytic leukemia [APL]).
2. Age ≥65 years.
3. Life expectancy of at least 12 weeks.
4. Patient is eligible for therapy with either decitabine or azacitidine.
5. ECOG performance status ≤2 .
6. The following baseline laboratory data:
● White blood cell (WBC) count <30,000/µL; use of hydroxyurea to control WBC is acceptable.
● Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert’s disease,
or direct bilirubin ≤ 2 x ULN if total bilirubin is abnormal.
● Serum creatinine ≤2.5 x ULN and estimated creatinine clearance ≥30 mL/min.
● Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.
7. Males who have partners of childbearing potential must agree to use 2 effective contraception methods
during the study and for 6 months following the last dose of study drug.
8. Patients must provide written informed consent.
Exclusion Criteria
1. AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or t(15;17).
2. Patients who are medically fit and willing to receive standard intensive induction chemotherapy
3. Patients who are candidates for allogeneic stem cell transplant at the time of enrollment.
4. Patients with a history of one of the following myeloproliferative neoplasms: essential thrombocythemia,
polycythemia vera, and primary myelofibrosis.
5. Received prior treatment with HMA or chemotherapy for antecedent MDS. Prior hydroxyurea or 6-
mercaptopurine is permitted, as is prior lenalidomide treatment for MDS.
6. History of allogeneic stem cell transplant.
7. Second malignancy requiring active systemic therapy within 1 year (except for hormonal/anti-hormonal
treatment, e.g., prostate or breast cancer).
8. Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal
fluid.
9. Any uncontrolled Grade 3 or higher (per NCI CTCAE, Version 4.03) viral, bacterial, or fungal infection
within 14 days prior to the first dose of study treatment. Antimicrobial prophylaxis or ongoing treatment of
resolving/controlled infection is permitted.
10. Patients with any of the following:
● Positive hepatitis B polymerase chain reaction (PCR) assay who have also tested positive for hepatitis
B surface antigen and/or anti-hepatitis B core antibody; patients with a negative PCR assay are
permitted with appropriate antiviral prophylaxis.
● Known or suspected active hepatitis C infection (positive by PCR or on antiviral therapy within the last
6 months).
● Known human immunodeficiency virus (HIV) infection.
11. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, or
myocardial infarction within 6 months prior to their first dose of study drug, or cardiac symptoms
consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose
of study treatment
12. Current therapy with other systemic anti-neoplastic or investigational agents, with the exception of
hydroxyurea.
13. Known hypersensitivity to any excipient contained in the drug formulation of any study treatment.
14. Any other condition which, in the opinion of the investigator, would compromise patient safety or interfere
with data interpretation.
2. Patients who are medically fit and willing to receive standard intensive induction chemotherapy
3. Patients who are candidates for allogeneic stem cell transplant at the time of enrollment.
4. Patients with a history of one of the following myeloproliferative neoplasms: essential thrombocythemia,
polycythemia vera, and primary myelofibrosis.
5. Received prior treatment with HMA or chemotherapy for antecedent MDS. Prior hydroxyurea or 6-
mercaptopurine is permitted, as is prior lenalidomide treatment for MDS.
6. History of allogeneic stem cell transplant.
7. Second malignancy requiring active systemic therapy within 1 year (except for hormonal/anti-hormonal
treatment, e.g., prostate or breast cancer).
8. Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal
fluid.
9. Any uncontrolled Grade 3 or higher (per NCI CTCAE, Version 4.03) viral, bacterial, or fungal infection
within 14 days prior to the first dose of study treatment. Antimicrobial prophylaxis or ongoing treatment of
resolving/controlled infection is permitted.
10. Patients with any of the following:
● Positive hepatitis B polymerase chain reaction (PCR) assay who have also tested positive for hepatitis
B surface antigen and/or anti-hepatitis B core antibody; patients with a negative PCR assay are
permitted with appropriate antiviral prophylaxis.
● Known or suspected active hepatitis C infection (positive by PCR or on antiviral therapy within the last
6 months).
● Known human immunodeficiency virus (HIV) infection.
11. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, or
myocardial infarction within 6 months prior to their first dose of study drug, or cardiac symptoms
consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose
of study treatment
12. Current therapy with other systemic anti-neoplastic or investigational agents, with the exception of
hydroxyurea.
13. Known hypersensitivity to any excipient contained in the drug formulation of any study treatment.
14. Any other condition which, in the opinion of the investigator, would compromise patient safety or interfere
with data interpretation.
The Estimated Number of Participants
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Taiwan
16 participants
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Global
500 participants
