Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Azacitidine

Decitabine

Immunomodulating Agents

Immunoglobulins

Antimetabolites

Enzyme Inhibitors

33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push

Volume equivalent to 10 mcg/kg, every 4 weeks via IV push

placebo

75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks

azacitidine

20 mg/m2 given IV x 5 days, every 4 weeks

decitabine

Phoenix Ho, MD

The purpose of this study in AML patients is to test whether vadastuximab talirine (SGN-CD33A; 33A) combined with either azacitidine or decitabine improves remission rates and extends overall survival as compared to placebo combined with either azacitidine or decitabine.

Hypomethylating agents (HMAs), such as decitabine or azacitidine, are considered a standard treatment for older patients with AML. The primary goals of this study are to test whether patients treated with an HMA (either decitabine or azacitidine) in combination with 33A will have better anti-tumor activity and/or survive longer than patients treated with an HMA in combination with placebo.

Patients who meet eligibility criteria will be randomly assigned to one of two treatment groups: 1) 33A plus HMA (Experimental Arm); or 2) placebo plus HMA (Comparator Arm). In addition to evaluating survival and remission rates, the minimal residual disease (MRD)-negative remission rate, duration of remission, event free- and leukemia-free survival, and safety and tolerability will be compared between arms.

Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute 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)

Time from randomization to death due to any cause

Number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) according to the modified response criteria for acute myeloid leukemia (AML) per Cheson 2003.

Number of patients who achieve both remission (CR or CRi) and MRD-negative status

Duration of remission is calculated from the first documentation of CR or CRi to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.

Event-free survival is calculated from the time of randomization to the first documentation of progression, relapse, or death, whichever comes first. Patients who do not have event (progression, relapse, or death) prior to analysis cutoff date are censored at the date of last response assessment. Patients who started another anticancer therapy before progression, relapse, or death are censored at the date of last response assessment prior to the start of new therapy. Patients who do not have response assessment post-baseline are censored at the date of randomization.

Leukemia-free survival is calculated from the first documentation of blast clearance (CR, CRi, mLFS) to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.

Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. SAE = serious adverse event. "Study treatment" in this data set refers to blinded study treatment.

Participants who experienced a laboratory grade increase to Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\], v4.03)

Time to CR or CRi is the time from randomization to the first documentation of CR/CRi

30- and 60-day survival from date of randomization. Estimated using Kaplan-Meier method.

Seagen Inc.

Treatment-emergent adverse events: a newly occurring or worsening adverse event after the first dose of study drug. Safety Analysis Set: 7 patients randomized to the HMA+33A received only HMA and are included in the HMA+Placebo safety set. 1 patient randomized to the HMA+placebo arm received 33A+HMA treatment. 1 patient in the HMA+placebo arm did not receive any study treatment.

33A plus azacitidine or decitabine

33A: 33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push

azacitidine: 75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks

decitabine: 20 mg/m2 given IV x 5 days, every 4 weeks

33A + HMA

placebo plus azacitidine or decitabine

placebo: Volume equivalent to 10 mcg/kg, every 4 weeks via IV push

azacitidine: 75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks

decitabine: 20 mg/m2 given IV x 5 days, every 4 weeks

Placebo + HMA

Total

Age, Continuous

Age Group

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Hungary

United States

Czechia

United Kingdom

Spain

South Korea

Austria

Belgium

Taiwan

Italy

Israel

France

Australia

Germany

Region of Enrollment

0=Normal activity; 1=Symptoms but ambulatory; 2=In bed less than 50% of the time; 3= In bed more than 50% of the time; 4=100% bedridden; 5=Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Chief Medical Officer

Overall Survival

Composite Complete Remission (CRc) Rate

MRD-negative CRc rate

MRD-negative CR rate

MRD-negative CRi rate

Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate

Patients who achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi).

Duration of Remission

Event-free Survival

Leukemia-free Survival

Patient with any TEAE

Patients with any AE related to study treatment

Patients with any SAE

Patients with any SAE related to study treatment

Patients with Grade 3 or Higher AE

Safety analysis set: 7 patients randomized to the HMA+33A received only HMA and are included in the HMA+Placebo safety set. 1 patient randomized to the HMA+placebo arm received 33A+HMA treatment. 1 patient in the HMA+placebo arm did not receive any study treatment.

Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events

Alanine Aminotransferase (IU/L) - High

Albumin (g/dL) - Low

Alkaline Phosphatase (IU/L) - High

Amylase (IU/L) - High

Aspartate Aminotransferase (IU/L) - High

Bilirubin (mg/dL) - High

Calcium (mg/dL) - Low

Creatinine (mg/dL) - High

Glucose (mg/dL) - High

Magnesium (mg/dL) - High

Phosphate (mg/dL) - Low

Potassium (mEq/L) - High

Potassium (mEq/L) - Low

Sodium (mEq/L) - Low

Triacylglycerol Lipase (IU/L) - High

Urate (mg/dL) - High

Hemoglobin (g/dL) - Low

Leukocytes (x10^3/uL) - High

Leukocytes (x10^3/uL) - Low

Lymphocytes (x10^3/uL) - High

Lymphocytes (x10^3/uL) - Low

Neutrophils (x10^3/uL) - Low

Platelets (x10^3/uL) - Low

Safety Analysis Set: 7 patients randomized to the HMA+33A received only HMA and are included in the HMA+Placebo safety set. 1 patient randomized to the HMA+placebo arm received 33A+HMA treatment. 1 patient in the HMA+placebo arm did not receive any study treatment.

Spots Global Cancer Trial Database for antigens, cluster of differentiation 33 (cd33)