Recruiting

Phase 1

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

Sponsor:

OHSU Knight Cancer Institute

Code:

NCT04659616

Conditions

Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspirate

Bone Marrow Biopsy

Cytarabine

Daunorubicin

Study Details

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.

Conditions

Acute Myeloid Leukemia

Study ID

NCT04659616

Start date

Jan 14, 2021

Status verified date

Jul, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

PRE-SCREENING INCLUSION CRITERIA: Ability to understand and the willingness to sign a written informed consent document
PRE-SCREENING INCLUSION CRITERIA: Age >= 18 years at time of informed consent. Both men and women of all races and ethnic groups will be included
PRE-SCREENING INCLUSION CRITERIA: Participants must consent to a bone marrow aspirate/biopsy that will be collected prior to start of planned 7+3 induction therapy. Patients with known favorable risk AML (2022 European Leukemia Net \[ELN\] Guidelines) or FLT3 mutations should not be pre-screened. If the risk category is unknown, then it is okay to pre-screen patients for study. Adverse or intermediate risk needs to be confirmed prior to treatment with pemigatinib (during screening period) as outlined below
TREATMENT INCLUSION CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
TREATMENT INCLUSION CRITERIA: For both the dose-determining and dose-expansion cohort, study population is limited to: Newly diagnosed, morphologically documented AML, based on the World Health Organization (WHO) 2008 classification, with wild-type FLT3 and cytogenetics or mutations associated with intermediate or adverse prognostic risk per European Leukemia Net (ELN) guidelines. These include:

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)
-5 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%
TREATMENT INCLUSION CRITERIA: Serum creatinine clearance >= 30 mL/min (as calculated by Cockcroft-Gault formula) (on or by day 8 of induction therapy, prior to starting pemigatinib)
TREATMENT INCLUSION CRITERIA: Serum phosphate within institutional upper limit of normal (ULN) or can be corrected with supplementation/ phosphate binders to be within institutional ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
TREATMENT INCLUSION CRITERIA: Serum electrolytes within institutional ULN: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected (on or by day 8 of induction therapy, prior to starting pemigatinib)
TREATMENT INCLUSION CRITERIA: Total serum bilirubin =< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
TREATMENT INCLUSION CRITERIA: Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
TREATMENT INCLUSION CRITERIA: Participants must consent to standard of care bone marrow aspirate/biopsies during treatment. Bone marrow biopsies will be obtained prior to study, on day 21 (+/- 3 days, if considered institutional standard of care), after recovery from induction therapy, and at the end of consolidation and/or prior to allogeneic stem cell transplant
TREATMENT INCLUSION CRITERIA: Female participants of childbearing potential must agree to use effective contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
TREATMENT INCLUSION CRITERIA: Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. The male participant must also refrain from sperm donation from the screening visit until 3 months following the last dose of study treatment

Exclusion Criteria:

PRE-SCREENING EXCLUSION CRITERIA: Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype) per WHO classification
PRE-SCREENING EXCLUSION CRITERIA: AML with FLT3 mutations that qualify for standard of care treatment with 7+3 and midostaurin (e.g. FLT3 ITD or TKD with allelic ratio > 0.05)
PRE-SCREENING EXCLUSION CRITERIA: Favorable risk AML: inv(16), t(8;21), NPM1 mutations without FLT3-ITD, or in-frame mutations (mono- or biallelic) affecting the basic leucine zipper region of CEBPA
PRE-SCREENING EXCLUSION CRITERIA: Any cancer-directed therapy within 2 weeks prior to starting planned 7+3 induction regimen, with the exception of hydroxyurea, which is allowed to control white blood cell count, or empiric all-trans retinoic acid (ATRA) for suspected APL
PRE-SCREENING EXCLUSION CRITERIA: Prior receipt of a selective FGFR inhibitor
PRE-SCREENING EXCLUSION CRITERIA: Known liver disease
PRE-SCREENING EXCLUSION CRITERIA: History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues

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)
PRE-SCREENING EXCLUSION CRITERIA: History of hypovitaminosis D being actively treated with supraphysiologic doses (e.g., 50,000 IU/weekly) to replenish the deficiency. Supraphysiologic doses of vitamin D need to be discontinued prior to starting pemigatinib. Vitamin D supplements are allowed
PRE-SCREENING EXCLUSION CRITERIA: Untreated human immunodeficiency virus (HIV) or active hepatitis C detectable by PCR, or chronic hepatitis B

Individuals positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIg) are eligible if HepB PCR is negative
PRE-SCREENING EXCLUSION CRITERIA: History of cerebrovascular accident or intracranial hemorrhage within 2 months of enrollment
PRE-SCREENING EXCLUSION CRITERIA: Unwillingness to receive infusion of blood products
PRE-SCREENING EXCLUSION CRITERIA: Inability to take oral medication
PRE-SCREENING EXCLUSION CRITERIA: Gastrointestinal condition/disorders that may raise gastric and/or small intestinal pH that could interfere with absorption, metabolism, or excretion of pemigatinib
PRE-SCREENING EXCLUSION CRITERIA: Known history and/or current evidence of ectopic mineralization/calcification, including (but not limited to): soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
PRE-SCREENING EXCLUSION CRITERIA: Concurrent active malignancy with expected survival of < 1 year
PRE-SCREENING EXCLUSION CRITERIA: Active central nervous system involvement with AML
TREATMENT EXCLUSION CRITERIA: Clinically significant coagulation abnormality (e.g., disseminated intravascular coagulation) that is present on or by day 8 of induction therapy prior to starting pemigatinib
TREATMENT EXCLUSION CRITERIA: Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of planned induction therapy, New York Heart Association class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed). History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.

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.
TREATMENT EXCLUSION CRITERIA: Left ventricular ejection fraction (LVEF) by echocardiogram < 45% prior to initiating pemigatinib
TREATMENT EXCLUSION CRITERIA: Active infection that is not well-controlled by antibacterial or antiviral therapy
TREATMENT EXCLUSION CRITERIA: Current use of prohibited medications including use of any potent CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug.

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
TREATMENT EXCLUSION CRITERIA: Current use of prohibited medication
TREATMENT EXCLUSION CRITERIA: Hypersensitivity to pemigatinib, or its excipients, when administered alone
TREATMENT EXCLUSION CRITERIA: Current evidence of corneal disorder/keratopathy, including (but not limited to): bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc., as confirmed by ophthalmologic examination.
TREATMENT EXCLUSION CRITERIA: Pregnancy or breastfeeding at the time of enrollment
TREATMENT EXCLUSION CRITERIA: Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol
TREATMENT EXCLUSION CRITERIA: Active central nervous system involvement with AML
TREATMENT EXCLUSION CRITERIA: Patients with FLT mutations

Study Design

Enrollment

32 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (cytarabine, daunorubicin, pemigatinib)

INDUCTION: Patients receive cytarabine IV on days 1-7, daunorubicin IV on days 1-3, and pemigatinib PO 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 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 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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bone Marrow Aspirate

Undergo bone marrow biopsy and aspirate

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiratie

Cytarabine

Given IV

Daunorubicin

Given IV

Electrocardiography

Undergo ECHO

Pemigatinib

Given PO

Primary outcome measure

Incidence of dose limiting toxicities (DLTs) [ Time Frame: From cycle 1 day 8, until 14 days after cycle 1 day 28 (up to 42 days) ]

Central Contacts and Locations

Central contacts

OHSU Knight Cancer Institute Clinical Trials Information

503-494-1080 trials@ohsu.edu

Locations

OHSU Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97239

Contacts

Elie Traer, MD PhD

503-494-3553 traere@ohsu.edu

Principal Investigator:

Elie Traer, MD PhD

UT Southwestern/Simmons Cancer Center-Dallas

Recruiting

Dallas, Texas, United States, 75390

Contacts

Yazan Madanat, MD

Yazan.Madanat@UTSouthwestern.edu

Principal Investigator:

Yazan Madanat, MD

More Information

Sponsor

OHSU Knight Cancer Institute

Last update posted

Jul 14, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by OHSU Knight Cancer Institute on 2026-07-14.