Acute Myeloid Leukemia, TP53 Gene Mutation
Conditions
Brief summary
Axatilimab combined with Decitabine/Venetoclax for the treatment of TP53-mutated/deleted AML patients
Interventions
DRUGDecitabine
20mg/m2/d x5 days (induction \& consolidation)
DRUGVenetoclax
400mg/d x14 days (induction); 400mg/d x7 days (consolidation)
DRUGAxatilimab
Dose escalation, given on Days 1 and 15 of each cycle
Sponsors
Northside Hospital, Inc.
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* MDS/AML or AML with a TP53 mutation or deletion, defined as: * greater than or equal to 10% AND (one of the following): * presence of a TP53 mutation * presence of a TP53 deletion by FISH * positive TP53 staining on IHC of diagnostic bone marrow * Either untreated or first salvage (primary refractory or first relapse)
Exclusion criteria
* KPS \<60 * active uncontrolled infection * history of HIV or active HBV or HBC infection * currently active second malignancy * calculated CrCl \<40mL/min * AST and/or ALT and/or direct bilirubin \>3x ULN * cardiac ejection fraction \<40% or history of uncontrolled cardiac arrhythmias * history of acute or chronic pancreatitis, history of myositis * known leukemia involvement of CNS * hematopoietic stem cell transplantation within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade 2+ related to the transplant * active acute or chronic GVHD requiring immunosuppressive treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Dose Level determination | 1 year | To find the recommended phase 2 dose (RP2D) of axatilimab when combined with decitabine and venetoclax by recording adverse events based on the CTCAE v.5. |
| Estimation of MRD-negative complete remission | 2 months | To estimate the MRD-negative complete remission rate after 1-2 cycles of induction chemotherapy with decitabine and venetoclax by conducing bone marrow biopsies and disease response assessments after induction |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimation of Response Rates, Overall Survival | 1 year | To estimate the complete response rate by evaluating bone marrow biopsies that occur after induction and every 3 months during consolidation |
| Evaluation of Safety of the Regimen | 1 year | To evaluate the safety and tolerability of axatilimab when combined with decitabine and venetoclax by recording all adverse events according to the CTCAE v5.0 |
| Estimation of Progression Free Survival | 1 year | To estimate the progression free survival rate by evaluating bone marrow biopsies that occur after induction and every 3 months during consolidation |
| Estimation of Overall Survival | 1 year | To estimate the overall survival rates by contacting patients 1 year after completion of therapy for survival data |
Countries
United States
Contacts
CONTACTScott R Solomon, MD
CONTACTCaitlin Guzowski
Outcome results
None listed