This phase II trial studies the side effects of olutasidenib when given together with different co-targeted therapies and to see how well it works in treating myeloid cell cancers in patients with a change (mutation) in the IDH1 gene and in a second gene (either the RAS, FLT3, or JAK-STAT pathway) (co-signaling mutation). The co-targeted therapy drug combinations studied in this trial include olutasidenib in combination with cladribine and cytarabine with or without venetoclax, olutasidenib in combination with gilteritinib with or without venetoclax, and olutasidenib in combination with ruxolitinib. Olutasidenib, gilteritinib, and ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as cladribine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving olutasidenib with co-targeted therapy may be safe, tolerable, and/or effective in treating myeloid cell cancers in patients with IDH1 and co-signaling gene mutations.
Additional locations may be listed on ClinicalTrials.gov for NCT07032727.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Courtney DiNardo
Phone: 713-794-1141
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of olutasidenib in combination with cladribine + low-dose cytarabine (LDAC) ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm 3) for patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation.
II. To quantify the composite complete remission rate (CRc; complete response [CR] + complete response with partial hematologic recovery [CRh] + compete response with incomplete count recovery [CRi]) in patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation treated with olutasidenib in combination with cladribine + LDAC ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm 3).
SECONDARY OBJECTIVES:
I. To determine overall survival (OS), event free survival (EFS), and duration of response (DOR) with olutasidenib in combination with a co-targeting chemotherapeutic agent.
II. To determine the overall response rate (ORR; CR + CRh + CRi + morphologic leukemia free state [MLFS] + partial response [PR]) of olutasidenib in combination with a co-targeting chemotherapeutic agent.
III. To evaluate occurrence of measurable residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation by polymerase chain reaction (PCR) and next generation sequencing (NGS)-based assays (e.g. IDH1 and FLT3 if applicable).
IV. To characterize the pharmacokinetic (PK) profiles of olutasidenib and venetoclax in plasma samples.
EXPLORATORY OBJECTIVE:
I. To investigate the clonal evolution in response to multiple targeted therapeutic agents using single cell sequencing of plasma and bone marrow samples at select sites.
OUTLINE: Patients with a RAS pathway co-mutation are assigned to arm 1, patients with a FLT3 pathway co-mutation are assigned to arm 2, and patients with a JAK-STAT pathway co-mutation are assigned to arm 3.
ARM 1: The first 16 patients enrolled are assigned to arm 1a and subsequent patients enrolled are assigned to arm 1b.
ARM 1A: Patients receive olutasidenib orally (PO) twice daily (BID) on days 1-28, cladribine intravenously (IV) on days 1-5, and LDAC subcutaneously (SC) on days 1-10 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM 1B: Patients receive olutasidenib PO BID on days 1-28, cladribine IV on days 1-5, LDAC SC on days 1-10, and venetoclax PO once daily (QD) on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM 2: The first 16 patients enrolled are assigned to arm 2a and subsequent patients enrolled are assigned to arm 2b.
ARM 2A: Patients receive olutasidenib PO BID and gilteritinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM 2B: Patients receive olutasidenib PO BID on days 1-28, gilteritinib PO QD on days 1-28, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM 3: Patients receive olutasidenib PO BID and ruxolitinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the trial.
After completion of study treatment, patients are followed up at 30-60 days and then every 3 months for 3 years.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorCourtney DiNardo
