A Safety Study of SGN-CD33A in Combination With Standard-of-care in Patients With AML

Study Overview
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Brief Summary
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This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) by itself (monotherapy) or in combination with other standard treatments. The main purpose of this study is to find the best dose and schedule for SGN-CD33A when given in combination with standard induction treatment, in combination with standard consolidation treatment, or by itself for maintenance treatment. This 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-leukemic activity of the study treatment will be assessed.

Detailed Description
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The study will be conducted in the following distinct parts: Part A: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 and Day 4 dosing) Part B: Consolidation dose escalation - consolidation combined with SGN-CD33A; up to 4 cycles of consolidation therapy will be administered after SGN-CD33A (Day 1 of each cycle). Part C: Maintenance - SGN-CD33A Monotherapy; Up to 24 patients with and up to 24 patient without prior allogeneic stem cell transplant will be treated with SGN-CD33A. Both arms will enroll simultaneously. SGN-CD33A will be administered on Day 1 of each 6-week cycle for up to 8 cycles. Part D: Induction plus consolidation - induction/consolidation combined with SGN-CD33A; patients who achieve a CR/CRi (with or without a second induction) will receive up to 4 cycles of consolidation therapy administered after SGN-CD33A (Day 1 of each cycle). Part E: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 dosing)

Official Title
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A Phase 1b Dose-escalation Study of SGN-CD33A in Combination With Standard-of-care for Patients With Newly Diagnosed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia, Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: Standard dose cytarabine for induction
* Drug: SGN-CD33A
* Drug: Daunorubicin
* Drug: High dose cytarabine for consolidation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subtypes of Acute Myeloid leukemia (except for acute promyelocytic leukemia) Eastern Cooperative Oncology Group status of 0 or 1 Adequate baseline renal and hepatic function Central venous access Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance Exclusion Criteria: Previous treatment for MDS or MPN for dose escalation cohorts Inadequate lung function Inadequate heart function

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: Induction with SGN-CD33A<br>7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A | Drug: Standard dose cytarabine for induction<br>* 100 mg/m2/day Days 1-7<br>Drug: SGN-CD33A<br>* Given intravenously Day 1 or Days 1 and 4 of each cycle<br>* Other names: vadastuximab talirine;Drug: Daunorubicin<br>* 60 mg/m2/day Days 1-3<br>|
| Experimental: Consolidation with SGN-CD33A<br>High dose cytarabine for consolidation + SGN-CD33A (28-day cycles) | Drug: SGN-CD33A<br>* Given intravenously Day 1 or Days 1 and 4 of each cycle<br>* Other names: vadastuximab talirine;Drug: High dose cytarabine for consolidation<br>* 3g/m2 on Days 1, 3, and 5 of each cycle<br>|
| Experimental: SGN-CD33A Maintenance<br>SGN-CD33A Monotherapy (42-day cycles) | Drug: SGN-CD33A<br>* Given intravenously Day 1 or Days 1 and 4 of each cycle<br>* Other names: vadastuximab talirine;|
| Experimental: Induction and Consolidation with SGN-CD33A<br>7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A | Drug: Standard dose cytarabine for induction<br>* 100 mg/m2/day Days 1-7<br>Drug: SGN-CD33A<br>* Given intravenously Day 1 or Days 1 and 4 of each cycle<br>* Other names: vadastuximab talirine;Drug: Daunorubicin<br>* 60 mg/m2/day Days 1-3<br>Drug: High dose cytarabine for consolidation<br>* 3g/m2 on Days 1, 3, and 5 of each cycle<br>|

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 | 
| Incidence of dose-limiting toxicity (DLT) |  | Through 1 month following last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) rate at the end of induction |  | Through 1 month following last dose | 
| Leukemia-free survival |  | Up to approximately 3 years | 
| Overall survival |  | Up to approximately 3 years | 
| Blood concentrations of SGN-CD33A and metabolites |  | Up to approximately 3 years | 
| Incidence of antitherapeutic antibodies (ATA) |  | Up to approximately 3 years | 
| Rate of minimal residual disease (MRD) clearance |  | 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, Drug Therapy, Acute Myelogenous Leukemia