This is a prospective, single-arm phase 2 pilot study to assess the response rate of IDH1 mutated relapsed/refractory acute myeloid leukemia (AML) patients who receive olutasidenib after progressing on venetoclax based regimens. Each cycle will last for 28 days. Patients will receive olutasidenib 150 mg orally twice daily Day 1 through Day 28. After 3 cycles of olutasidenib, azacitidine 75 mg/m2 given on Day 1 through Day 7 may be added at the discretion of the treating investigator if the patient has not achieved a complete remission. Subjects with at least a PR after 6 cycles of treatment will continue treatment as previously described. Subjects without at least a partial response (PR) after 6 cycles of treatment will move to long term follow up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Olutasidenib 150 mg orally twice a day
Azacitidine 75 mg/m2 subcutaneously or IV (over 10-40 minutes)
Atrium Health Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
RECRUITINGComposite complete remission rate
Composite complete remission (CRc) rate is defined as patients that meet the criteria for CR + CRh + CRi per the modified European LeukemiaNet (mELN) 2022. * Complete Remission (CR) is defined as absence of leukemia cells in the bone marrow (\< 5% blasts), normal blood counts (absolute neutrophil count ≥ 1000/μL and platelet count ≥ 100,000/μL), and the absence of circulating blasts, and extramedullary disease * Complete Remission with Hematologic recovery (CRh) is defined as meeting all criteria for CR as Bone marrow myeloblasts \< 5%; absence of circulating blasts; absence of extramedullary disease; both ANC ≥ 0.5x109/L (500/µL) and platelet count ≥ 50×109/L (50 000/µL) * Complete Remission with Incomplete hematologic recovery (CRi) is defined as meeting all criteria for Complete Remission (CR) except for either a low neutrophil count (neutropenia) or a low platelet count (thrombocytopenia)
Time frame: 2 years
Overall response rate (ORR)
ORR is defined as the proportion of patients achieving CR + CRh + CRi + Partial Remission (PR) + morphologic leukemia-free state \[MLFS\] per ELN 2022. PR is defined as all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%. MLFS is defined as bone marrow blasts \< 5%, absence of circulating blasts, and no hematologic recovery.
Time frame: 2 years
Overall survival
OS is defined as the time from registration to death from any cause or last known follow-up.
Time frame: 2 years
Duration of response (DoR)
DoR is defined as the time between the first achieved response (CR, CRh, CRi, PR, MLFS) and the earliest evidence of relapse (blasts ≥ 5%) per ELN 2022 or death or date of last follow up.
Time frame: 2 years
Time to hematologic improvement (hemoglobin)
Improvement of Hgb is defined as the time it takes for an individual's hemoglobin level to increase by ≥ 1g/dL from Cycle 1 Day 1 without transfusion
Time frame: 2 years
Time to hematologic improvement (platelet count)
Improvement of PLT is defined as the time it takes for an individual's platelet count to increase by ≥ 50 x 10\^9/L from Cycle 1 Day 1 without transfusion
Time frame: 2 years
Time to hematologic improvement (neutrophil count)
Improvement of ANC is defined as the time it takes for an individual's neutrophil count to increase to ≥ 1,500 cells/µL for 3 days.
Time frame: 2 years
Rate of transfusion independence
The rate of transfusion independence is defined as the absence of red blood cell (RBC) transfusions for ≥ 8 weeks following the start of treatment
Time frame: 2 years
Rate of allogeneic transplant
The rate of allogeneic transplant is defined as the proportion of patients who undergo allogeneic transplant following response to olutasidenib.
Time frame: 2 years
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