RecruitingPhase 1NCT04659616

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia

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

Sponsor

OHSU Knight Cancer Institute

Enrollment

32 participants

Start Date

Jan 14, 2021

Study Type

INTERVENTIONAL

Conditions

Acute Myeloid Leukemia

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria19

t(9;11)(p21.3;q23.3); MLLT3-KMT2A
Cytogenetic abnormalities not classified as favorable
t(6;9)(p23;q34.1); DEK-NUP214
t(v;11q23.3); KMT2A rearranged
t(9;22)(q34.1;q11.2); BCR-ABL1
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)
or del(5q); -7; -17/abn(17p)
Complex karyotype - defined as three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1
Monosomal karyotype - defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor AML)
Mutated RUNX1 (without favorable risk cytogenetics/mutations)
Mutated BCOR (without favorable risk cytogenetics/mutations)
Mutated EZH2 (without favorable risk cytogenetics/mutations)
Mutated ASXL1 (without favorable risk cytogenetics/mutations)
Mutated SF3B1 (without favorable risk cytogenetics/mutations)
Mutated SRSF2 (without favorable risk cytogenetics/mutations)
Mutated STAG2 (without favorable risk cytogenetics/mutations)
Mutated U2AF1, (without favorable risk cytogenetics/mutations)
Mutated ZRSR2 (without favorable risk cytogenetics/mutations)
Mutated TP53 (mono- or biallelic) at a variant allele fraction of at least 10%

Exclusion Criteria7

Except for commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
Individuals positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIg) are eligible if HepB PCR is negative
A screening QT interval by Fridericia's Correction Formula (QTcF) interval \> 480 ms will result in exclusion.
For participants with an intraventricular conduction delay (QRS interval \> 120 ms), the JTc interval may be used in place of the QTc with approval from Sponsor-Investigator. The JTc must be =\< 340 ms if JTc is used in place of the QTc.
Use of CYP3A4 inhibitors should be avoided but, if medically necessary, is permitted with a dose reduction of study drug
Use of moderate CYP3A4 inhibitors are permitted.
Based on the low overall bioavailability of topical ketoconazole, there are no restrictions on topical ketoconazole