Acute Myelogenous Leukemia, Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, Antibody-Drug Conjugate, CD33 Antigen, Drug Therapy, Acute Myelogenous Leukemia
Brief summary
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
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)
Interventions
DRUGStandard dose cytarabine for induction
100 mg/m2/day Days 1-7
DRUGSGN-CD33A
Given intravenously Day 1 or Days 1 and 4 of each cycle
DRUGDaunorubicin
60 mg/m2/day Days 1-3
DRUGHigh dose cytarabine for consolidation
3g/m2 on Days 1, 3, and 5 of each cycle
Sponsors
Seagen Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Blood concentrations of SGN-CD33A and metabolites | Up to approximately 3 years |
| Complete remission (CR) rate at the end of induction | Through 1 month following last dose |
| Rate of minimal residual disease (MRD) clearance | Up to approximately 3 years |
| Incidence of antitherapeutic antibodies (ATA) | Up to approximately 3 years |
| Leukemia-free survival | Up to approximately 3 years |
| Overall survival | Up to approximately 3 years |
Countries
United States
Outcome results
None listed