Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute Promyelocytic Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, Antibody-Drug Conjugate, CD33 Antigen, Immunotherapy, Drug Therapy, Acute Myelogenous Leukemia, Acute Promyelocytic Leukemia, APL
Brief summary
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
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.
Interventions
DRUGHMA
azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days
DRUGSGN-CD33A
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)
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
* 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)
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 |
Secondary
| Measure | Time frame |
|---|---|
| Rate of complete remission | Up to 3 months |
| Duration of complete remission | Up to approximately 3 years |
| Blood concentrations of SGN-CD33A and metabolites | Through 3 weeks after dosing |
| Overall survival | Up to approximately 3 years |
| Relapse-free survival | Up to approximately 3 years |
| Incidence of antitherapeutic antibodies | Through 1 month following last dose |
Countries
United States
Outcome results
None listed