Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia
brief summary
This phase I trial identifies the best dose and clinical benefit of giving pemigatinib following standard induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Pemigatinib selectively inhibits FGFR (fibroblast growth factor receptor) activity, a receptor that may contribute to the growth of leukemia cells. The genetic changes responsible for activating the growth of leukemia cells can be unique to each patient and can change during the course of the disease. Chemotherapy drugs, such as cytarabine and daunorubicin 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.
detailed description
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose of pemigatinib (INC054828) following standard of care induction chemotherapy.
SECONDARY OBJECTIVES:
I. To assess preliminary efficacy associated with study intervention. II. To assess the safety profile of the study intervention. III. To evaluate time-to- marrow recovery between cycles of pemigatinib.
EXPLORATORY OBJECTIVES:
I. Assess minimal residual disease (MRD) by fluorescent in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and/or next-generation sequencing of acute myeloid leukemia (AML) genetic abnormalities in bone marrow and blood.
II. Quantify FGF2/FGFR immunohistochemical staining of marrow core biopsies and compare to historical controls at various timepoints.
III. Assess ex vivo sensitivity of patient-derived mononuclear cells to pemigatinib with and without FGF2 supplementation.
IV. Evaluate pemigatinib-induced changes in stromal expression using cultured bone marrow samples and compare to historical controls.
V. Evaluate the impact of pemigatinib on the need for intravenous (IV) phosphate replacement after chemotherapy.
OUTLINE: This is a dose-escalation study of pemigatinib followed by a dose-expansion study.
INDUCTION: Patients receive cytarabine IV on days 1-7, daunorubicin IV on days 1-3, and pemigatinib orally (PO) once daily (QD) on days 8-21 in the absence of disease progression or unacceptable toxicity. Patients with hematologic count recovery (assessed between days 25-42) after induction proceed to consolidation therapy. Patients undergo echocardiography (ECHO) during screening and as clinically indicated on study. Patients undergo blood sample collection and bone marrow aspirate and biopsy during screening and cycle 11 day 21 on study.
CONSOLIDATION: Patients receive high dose cytarabine IV twice daily (BID) on days 1, 3, and 5 of each cycle, and pemigatinib PO QD on days 8-21 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression of unacceptable toxicity. Patients undergo ECHO as clinically indicated and blood sample collection and bone marrow biopsy and aspirate at the end of consolidation.
official title
A Multicenter, Phase 1, Open-Label Study of the FGFR Inhibitor Pemigatinib (INCB054828) Administered After Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) With Adverse or Intermediate Risk Cytogenetics