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Label indication Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . FDA label
Olutasidenib · 3 trials · 21 indications
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)
The number of participants experiencing excessive toxicity in six (6) patient safety lead-in over the duration of study treatment will be reported. All treatment-emergent adverse events (TEAEs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Composite complete remission (CRc) among participants will be reported as a percentage. CRc is includes number of participants experiencing complete remission \[CR\], complete remission with partial hematologic recovery \[CRh\] or complete remission with incomplete hematologic recovery \[CRi\] after up to 3 cycles as defined by modified 2022 European LeukemiaNet (ELN) criteria.
To identify the dose of olutasidenib that is feasible when given post-RT in combination with temozolomide as maintenance therapy in pediatric and young adult patients newly diagnosed with IDH1-mutant high-grade glioma
To assess the post-RT efficacy of olutasidenib in newly diagnosed patients with WHO Grade 3 IDH1-mutant Astrocytoma treated with maintenance olutasidenib and temozolomide for 13 cycles followed by 13 cycles of single agent olutasidenib compared to molecularly-stratified and matched historical controls
To characterize the plasma pharmacokinetic (PK) properties of olutasidenib in pediatric patients (e.g., 12 to \< 18 years of age), administered in combination with temozolomide (first year) and as single agent (second year) as maintenance chemotherapy by measuring the Maximum Concentration \[Cmax\] and Area Under the Curve (AUC) of olutasidenib in plasma (All strata).
| Arm | Type | Description |
|---|---|---|
| Olutasidenib and Azacitidine | EXPERIMENTAL | 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 or for whom loss of response is suspected. Subjects with at least a PR after 6 cycles of treatment will continue treatment.. Subjects without at least a PR after 6 cycles of treatment will move to long term follow up. |
| OLUVENAZA Treatment Group | EXPERIMENTAL | Participants in this group will receive combination treatment of Olutasidenib, Venetoclax and Azacitidine orally for up to 12 cycles, each cycle lasting 28 days. Total participation duration is about 14 months |
| Stratum A | EXPERIMENTAL | Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3. |
| Stratum B | EXPERIMENTAL | Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4. |
| Stratum C | EXPERIMENTAL | Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG. |
| Name | Type | Description |
|---|---|---|
| Olutasidenib | DRUG | Olutasidenib 150 mg orally twice a day |
| Azacitidine (AZA) | DRUG | Azacitidine 75 mg/m2 subcutaneously or IV (over 10-40 minutes) |
| Venetoclax | DRUG | Participants will receive Venetoclax as a 100mg tablet to be self-administered orally with a meal and water once daily, two hours after starting Olutasidenib administration, starting on Cycle 1 Day 1. The dosing regimen of Venetoclax is as follows: * Cycle 1: Days 1 - 21 over a 28-day cycle * Cycle 1 Week 1: Ramp-up dosing schedule up to 400mg (4 x 100mg/tablet) * For participants with blast clearance: Cycle 2 and beyond: Days 1 - 14 over a 28-day cycle * For participants with persistent clearance: Cycle 2 through 4: Days 1 - 21 |
| Azacitidine | DRUG | Participants will receive Azacitidine 75 mg/m2 per day via subcutaneous (SC) injection or intravenous (IV) infusion on Days 1-7 of each cycle. |
| Olutasidenib + TMZ | DRUG | Olutasidenib 150 mg PO BID + Temozolomide 200 mg/m2 PO QD |
Inclusion Criteria: 1. 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. 2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of...
Olutasidenib is an investigational small-molecule IDH1 inhibitor being developed by Rigel Pharmaceuticals, Inc. (ticker RIGL) for cancers that carry an IDH1 mutation, including acute myeloid leukemia and high grade glioma. It is in Phase 2 clinical development and is being studied both as a single agent and in combination regimens.
Olutasidenib is being studied in IDH1-mutated acute myeloid leukemia, including relapsed or refractory disease after prior venetoclax and newly diagnosed disease in patients eligible for intensive induction chemotherapy. In the newly diagnosed setting it is tested with venetoclax and azacitidine. These uses are investigational and remain in Phase 2 testing.
Olutasidenib targets mutant IDH1, the isocitrate dehydrogenase 1 enzyme. It is an IDH1 inhibitor, and the clinical programs select patients whose tumors carry IDH1 mutations, including specific variants such as IDH1 R132C, R132H, R132S, R132G and R132L. Its development spans IDH1-mutated acute myeloid leukemia and IDH1-mutant high grade glioma.
Olutasidenib is developed by Rigel Pharmaceuticals, Inc., which trades under the ticker RIGL. Rigel is the sponsor of the Phase 2 studies evaluating olutasidenib in IDH1-mutated acute myeloid leukemia and in high grade glioma, including a combination study with temozolomide.
Olutasidenib is in Phase 2 clinical development. It is investigational and is being evaluated in recruiting Phase 2 trials in IDH1-mutated acute myeloid leukemia and IDH1-mutant high grade glioma. The studies are open-label and uncontrolled, and enrollment is limited to adults and, in the glioma study, patients aged 12 years and older.
Olutasidenib is being studied in three recruiting Phase 2 trials: NCT07471841 in relapsed IDH1-mutated AML after prior venetoclax, NCT06782542 combining olutasidenib with venetoclax and azacitidine in newly diagnosed IDH1-mutated AML, and NCT06161974 testing olutasidenib with temozolomide in high grade glioma across the United States, Australia, Canada, Germany, the Netherlands, New Zealand and the United Kingdom.