A Safety Study of SGN-CD33A in AML Patients

Study Overview
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Brief Summary
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This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) administered as a single agent and in combination with a hypomethylating agent (HMA). The main purpose of the study is to find the maximum tolerated dose (MTD, which is the highest dose that does not cause unacceptable side effects) of SGN-CD33A in patients with acute myeloid leukemia (AML). The MTD will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemia activity of SGN-CD33A will be assessed.

Detailed Description
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This study will explore SGN-CD33A as a monotherapy and in combination with a hypomethylating agent (HMA; i.e., azacitidine or decitabine). Initial study treatment with SGN-CD33A includes a maximum of 2 cycles of treatment for monotherapy and 4 cycles for combination cohorts. Patients who achieve documented CR or CRi (Monotherapy) or clinical benefit (Combination) during the first part of the study are eligible to continue treatment. Additional monotherapy cohorts may include patients with relapsed acute promyelocytic leukemia, relapsed patients with nucleophosmin-1 gene mutation (absence of fms-like tyrosine kinase 3 mutation) (NPM1-mutated, FLT-3 wild type), alternate dosing schedules (fractionated dosing on Days 1 and 4), treatment naive patients with AML who declined intensive therapy, and patients who have relapsed after post-allogeneic stem cell transplant. Patients in the combination cohort will be treated with azacitidine or decitabine per institutional practice prior to SGN-CD33A dosing. Expansion cohorts may be added for further evaluation of safety, pharmacokinetics, pharmacodynamics, and antitumor activity.

Official Title
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A Phase 1 Trial of SGN-CD33A in Patients With CD33-positive Acute Myeloid Leukemia

Conditions
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Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Promyelocytic Leukemia

Intervention / Treatment
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* Drug: HMA
* Drug: SGN-CD33A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myeloid leukemia, positive for CD33 Eastern Cooperative Oncology Group status of 0 or 1 Adequate baseline renal and hepatic function Central venous access Either achieved complete remission (greater than 12 weeks in duration) with initial induction/consolidation and have experienced relapse of disease or declined treatment with high-dose induction/consolidation Bone marrow blasts greater than or equal to 5% for relapsed patients, or greater than or equal to 20% for untreated patients Exclusion Criteria: Inadequate lung function Prior allogeneic stem cell transplant, except for a specific cohort High-dose chemotherapy within 4 weeks of study drug Antileukemia treatment within 14 days of study drug (other than hydroxyurea or 6-mercaptopurine)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-CD33A + HMA<br>SGN-CD33A with hypomethylating agent | Drug: HMA<br>* azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days<br>Drug: SGN-CD33A<br>* Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)<br>* Other names: vadastuximab talirine;|
| Experimental: SGN-CD33A Monotherapy<br>SGN-CD33A | Drug: SGN-CD33A<br>* Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)<br>* Other names: vadastuximab talirine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Through 1 month following last dose | 
| Incidence of laboratory abnormalities |  | Through 1 month following last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood concentrations of SGN-CD33A and metabolites |  | Through 3 weeks after dosing | 
| Incidence of antitherapeutic antibodies |  | Through 1 month following last dose | 
| Rate of complete remission |  | Up to 3 months | 
| Duration of complete remission |  | Up to approximately 3 years | 
| Relapse-free survival |  | Up to approximately 3 years | 
| Overall survival |  | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, Antibody-Drug Conjugate, CD33 Antigen, Immunotherapy, Drug Therapy, Acute Myelogenous Leukemia, Acute Promyelocytic Leukemia, APL