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Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax

ConditionsIDH1 MutationRelapsed / Refractory AML
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorTimothy Pardee

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Age ≥ 18 years at the time of consent.

ECOG Performance Status of ≤ 2 within 28 days prior to registration.

Must have histologically or cytologically documented relapsed and/or refractory Acute Myeloid Leukemia (Refractory is defined as failure to achieve a CR after induction chemotherapy or a minimum of two cycles of HMA plus venetoclax)

Disqualifiers

Previous exposure to ivosidenib or any IDH1 inhibitor.

Active infection requiring IV systemic therapy. NOTE: Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

Known CNS involvement with AML.

Previous allogeneic stem cell transplant within 60 days prior to registration.

Trial design

Design model

Single group

Treatments tested in this trial

  • Olutasidenib

    Drug

    Olutasidenib 150 mg orally twice a day

  • Azacitidine (AZA)

    Drug

    Azacitidine 75 mg/m2 subcutaneously or IV (over 10-40 minutes)

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Olutasidenib and AzacitidineExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Composite 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

Secondary outcomes

1

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
2

Overall survival

OS is defined as the time from registration to death from any cause or last known follow-up.

Time frame
2 years
3

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
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Timothy Pardee

Lead sponsor

Hoosier Cancer Research Network

Sponsor institution

Atrium Health Wake Forest Baptist

Collaborator

Rigel Pharmaceuticals

Collaborator

Source ClinicalTrials.gov
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