Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
Conditions
Keywords
navtemadlin
Brief summary
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, when administered alone and in combination with low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be relapsed/refractory (having failed prior therapy) and will be assigned to receive monotherapy (KRT-232 alone) or combination therapy (KRT-232 with LDAC or KRT-232 with Decitabine).
Interventions
DRUGKRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
DRUGCytarabine
Cytarabine is an anti-cancer chemotherapy drug taken via injection.
DRUGDecitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Part A: Patients with relapsed or refractory AML, or newly-diagnosed AML secondary to MPN * Part B:Patients with relapsed or refractory AML secondary to MPN (myelofibrosis \[MF\], polycythemia vera \[PV\], or essential thrombocythemia \[ET\]); patients may have been treated with ≥1 prior lines of therapy for their AML secondary to MPN. * Adequate hepatic and renal function * Appropriate prior treatment with an FLT3 or IDH1/2 inhibitor where applicable Key
Exclusion criteria
* Patients who are TP53 mutation positive * Prior treatment with an MDM2 antagonist therapy * Patients treated with ≥ 18 g/m2 of cytarabine within the prior 90 days are not eligible to be treated with cytarabine on this study but may be treated with decitabine (for Part A) . * Patients previously treated with decitabine are not eligible to receive decitabine on this study but may be treated with cytarabine (for Part A) . * Patients who have received an allogeneic HSCT within 90 days of enrollment or who have active graft-versus-host disease requiring active therapy (for Part A) * Allogeneic stem cell transplant within 3 months; autologous stem cell transplant within 3 months or active graft-versus-host disease prior to first dose of study treatment (for Part B) * Patients who have received immunosuppressive therapy for graft-versus-host disease within 1 month prior to enrollment into this study * Patients who are eligible for an allogeneic HSCT per the opinion of the investigator and have a donor. Patients who are HSCT-eligible in the opinion of the investigator, but who refuse a transplant, are eligible for the study. * Patients with known CNS involvement with AML, acute promyelocytic leukemia (APL), or a history of bleeding diathesis * Patients who have had major surgery within 28 days prior to the first treatment with KRT-232 * Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: To determine KRT-232 recommended phase 2 dose (RP2D) | 28 Days | Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine |
| Part B: To determine the RP2D of KRT-232 | 2 years after last patient enrolled | The safety review committee (SRC) will determine the RP2D based on safety and tolerability data obtained from each arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh) | 12 weeks | Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria |
| Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi) | 12 weeks | Proportion of patients achieving complete remission (CR), complete remission with partial hematological improvement (CRh), and CR with incomplete hematologic recovery (CRi) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria |
Countries
Australia, Belgium, France, Germany, Hungary, Israel, Italy, Poland, South Korea, Spain, United Kingdom, United States
Outcome results
None listed