Pemigatinib for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By OHSU Knight Cancer Institute Clinical Trials Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OHSU Knight Cancer Institute

Must not be taking: FGFR inhibitors, CYP3A4 inducers

Disqualifiers: Acute promyelocytic leukemia, FLT3 mutations, Liver disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and potential benefits of adding pemigatinib, a drug that targets specific cancer cell growth signals, to standard chemotherapy for individuals with newly diagnosed acute myeloid leukemia (AML). The study combines pemigatinib with common chemotherapy drugs, cytarabine (also known as Cytosar-U, Depocyt, or Tarabine PFS) and daunorubicin (also known as Daunomycin, Rubidomycin, or Cerubidine), to assess whether this combination can more effectively halt the growth of leukemia cells. Patients newly diagnosed with AML, without certain genetic mutations, and experiencing everyday impacts from their leukemia might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications that strongly affect liver enzymes (CYP3A4 inducers) within 14 days before starting the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pemigatinib is generally well-tolerated. The FDA has approved it for other uses, indicating reasonable safety. In earlier studies, some patients experienced side effects, but these were manageable. Common side effects included changes in blood test results and mild digestive issues, while serious side effects were rare.

Cytarabine and daunorubicin, the other drugs in this trial, are also well-known in cancer treatment. They can cause side effects like low blood cell counts and nausea, but doctors typically monitor and manage these.

Overall, the safety information for pemigatinib and the other drugs in this trial appears promising. However, this trial aims to better understand any specific risks or benefits of using pemigatinib with these other treatments for leukemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for acute myeloid leukemia (AML), which typically includes chemotherapy drugs like cytarabine and daunorubicin, pemigatinib introduces a novel approach by targeting specific genetic mutations. Researchers are excited about pemigatinib because it works as a fibroblast growth factor receptor (FGFR) inhibitor. This mechanism specifically targets cancer cells with FGFR mutations, potentially leading to more effective treatment outcomes. By honing in on these genetic abnormalities, pemigatinib could offer a more personalized and potentially more effective option for patients with AML, distinguishing it from the more generalized action of traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that pemigatinib effectively targets certain cancer pathways by blocking FGFR, a protein that may aid leukemia cell growth. Studies on similar cancer types have demonstrated high rates of complete response, with many patients experiencing significant shrinkage or disappearance of their cancer. Pemigatinib has received approval for other conditions, proving its efficacy in stopping cancer cell growth. In this trial, participants will receive a combination treatment of cytarabine, daunorubicin, and pemigatinib to evaluate its potential effectiveness for acute myeloid leukemia (AML). Although direct data on pemigatinib's use for AML is limited, the drug's mechanism suggests it could be promising for treating AML. ^{1 2 3 6 7}

Who Is on the Research Team?

Elie Traer, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

Adults with newly diagnosed acute myeloid leukemia (AML) who have specific genetic changes linked to a poor prognosis can join this trial. They must be able to consent, perform daily activities with minimal help (ECOG 0-2), and have adequate organ function. Pregnant or breastfeeding women, those with favorable risk AML, recent cancer therapy except hydroxyurea, prior FGFR inhibitor use, certain infections or diseases affecting mineral balance are excluded.

Inclusion Criteria

My cancer has specific genetic changes known as inv(3) or t(3;3).

My kidney function, measured by creatinine clearance, is adequate.

I agree to use or have my partner use two forms of birth control during and for 3 months after the study.

Exclusion Criteria

I have been diagnosed with a specific type of leukemia called APL.

I cannot take medicine by mouth.

I haven't had cancer treatment in the last 2 weeks, except for hydroxyurea or ATRA.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive cytarabine IV on days 1-7, daunorubicin IV on days 1-3, and pemigatinib PO QD on days 8-21

6 weeks

Multiple visits (in-person)

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

16 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Pemigatinib

Trial Overview The trial is testing the effectiveness of pemigatinib following standard chemotherapy in treating AML. Pemigatinib targets FGFR activity which may drive leukemia growth. Participants will first receive cytarabine and daunorubicin chemotherapy before starting on pemigatinib at a dose determined safe and potentially beneficial.

How Is the Trial Designed?

Group I: Treatment (cytarabine, daunorubicin, pemigatinib) Experimental Treatment 7 Interventions

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.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Current frontline treatments for acute myeloid leukemia (AML) using ara-C and topoisomerase II agents achieve complete response rates of 70%, but long-term survival remains low at 25%.

Newer agents like nucleoside analogs and hypomethylating agents show promise, with combination therapies yielding higher complete response rates, particularly when used alongside traditional treatments like ara-C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New chemotherapeutic agents in acute myeloid leukemia. Kantarjian, HM., Estey, EH., Keating, MA.[2013]

In a study involving five patients with therapy-related acute myeloid leukemia, a combination of idarubicin, high-dose cytarabine, and etoposide achieved complete remission in all patients after just one course of treatment.

The treatment was well-tolerated, with low levels of toxicity and no deaths during the induction therapy, suggesting it is a promising option for inducing remission in secondary acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idarubicin, high-dose cytarabine and etoposide for remission induction in therapy-related acute myeloid leukemia. Philpott, N., Mehta, J., Treleaven, J., et al.[2019]

Acute myeloid leukemia (AML) treatment has seen little change in 40 years, but new agents like IDH inhibitors and antibody-drug conjugates show promise in improving outcomes, either alone or with traditional chemotherapy.

A variety of novel therapies, including cytotoxic agents, epigenetic modifiers, and targeted inhibitors, are currently being tested in clinical trials, indicating a potential shift in AML management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for acute myeloid leukemia. Saygin, C., Carraway, HE.[2023]

The study found significant variations in how acute myeloid leukemia (AML) patients respond to the chemotherapy drug cytarabine (Ara-C), with some patients being sensitive and others resistant based on their gene expression profiles.

Higher expression levels of certain genes like deoxycytidine kinase (DCK) and ribonucleotide reductase M1 (RRM1) were associated with better treatment outcomes, while a newly proposed Ara-C resistance index (RI) could help predict drug response and potential treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia. Abraham, A., Varatharajan, S., Karathedath, S., et al.[2022]

In a study of 327 adult patients with acute myeloid leukaemia (AML), 82% achieved complete remission after receiving idarubicin- and cytarabine-based intensive chemotherapy, indicating the regimen's effectiveness for this age group.

Patients with favourable karyotypes had significantly better long-term outcomes, with a 5-year survival rate of 71%, while those with adverse karyotypes had only an 8% survival rate, highlighting the need for new treatment strategies for patients with poorer genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of intensive chemotherapy for adults with de novo acute myeloid leukaemia (AML): the nationwide AML-92 study by the Finnish Leukaemia Group. Koistinen, P., Räty, R., Itälä, M., et al.[2007]

In a study of 24 patients with acute myeloid leukemia (AML) treated with a combination of idarubicin, cytarabine, and cladribine (ICC), 79.2% achieved complete remission (CR), indicating a high efficacy of this treatment regimen.

The study also reported a 33-month overall survival rate of 56% and a disease-free survival rate of 36%, suggesting that ICC can be an effective induction therapy, especially in high-risk AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of Acute Myeloid Leukemia with Idarubicin, Cytarabine and Cladribine. Wiedower, E., Jamy, O., Martin, MG.[2015]

In a study of 70 adult patients with acute myelogenous leukemia (AML), high-dose cytarabine followed by daunorubicin achieved a complete remission (CR) rate of 90%, indicating strong efficacy for this treatment regimen.

While the treatment showed significant antileukemic activity, it also resulted in notable toxicity, including severe cerebellar toxicity in some patients, highlighting the need for careful management and further research to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults. Phillips, GL., Reece, DE., Shepherd, JD., et al.[2021]

The DAF regimen, which includes daunorubicin, fludarabine, and cytarabine, showed a 56% overall response rate in 34 patients with relapsed or refractory acute myeloid leukemia (AML), with 15 out of 16 patients achieving complete remission after the first course.

The treatment was well tolerated, with severe neutropenia and serious infections occurring in a significant number of patients, but no severe long-term complications like liver or kidney failure were observed, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study. Hołowiecki, J., Grosicki, S., Kyrcz-Krzemien, S., et al.[2013]

Intensive research is being conducted to understand and overcome resistance to chemotherapy in acute myeloid leukemia (AML), particularly focusing on the drugs daunorubicin and cytarabine, which are currently the most effective treatments.

Current studies are exploring ways to enhance the effectiveness of cytarabine by improving its delivery to leukemic cells and increasing the number of cells in the S-phase of the cell cycle, which may lead to better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and pharmacologic aspects of drug resistance in acute myeloid leukemia. Ross, DD.[2019]

The combination of 5-Aza-2'-deoxycytidine (DAC) and cytarabine (ara-C) demonstrated either additive or synergistic effects on cell death in various human leukemia cell lines, indicating a potential for enhanced efficacy in treating acute myeloid leukemia.

While DAC and ara-C together increased cell death, they exhibited antagonistic effects on epigenetic regulation, suggesting that hypomethylated cells may be more sensitive to ara-C, which could inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cytarabine and decitabine in combination in human leukemic cell lines. Qin, T., Youssef, EM., Jelinek, J., et al.[2022]

In a study of 43 patients under 60 years old with untreated acute myeloid leukemia, the combination of idarubicin, etoposide, and carboplatin achieved a remission rate of 67% with a median leukemia-free survival of 15.4 months.

The treatment was associated with significant mucosal toxicity, including severe gastrointestinal side effects in a substantial number of patients, indicating that while effective, the regimen's tolerability may need improvement through adjustments in postremission therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin. Bow, EJ., Gallant, G., Williams, GJ., et al.[2015]

In a study of 125 patients with de novo acute myeloid leukemia, idarubicin combined with cytarabine resulted in a significantly higher complete remission rate (82.1%) compared to daunorubicin (41.2%) in patients with high MDR1 expression.

Idarubicin also showed superior efficacy in high MDR1 expressers with favorable or intermediate risk, while no significant differences were observed between the two treatments in low MDR1 expressers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idarubicin is superior to daunorubicin in remission induction of de novo acute myeloid leukemia patients with high MDR1 expression. Shi, P., Zha, J., Guo, X., et al.[2018]

In a study of adult patients with acute myeloid leukemia (AML) receiving the '7 + 3' induction therapy, 59% achieved remission, but many required multiple induction courses, leading to prolonged myelosuppression and increased infection rates.

High-dose cytarabine (HDARA-C) consolidation significantly improved disease-free survival for patients who achieved remission, while the myelosuppression and infection risks were comparable to those seen with single induction courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome. Bow, EJ., Kilpatrick, MG., Scott, BA., et al.[2019]

Recent advancements in acute myeloid leukemia (AML) treatment have introduced new drugs like gemtuzumab and midostaurin, which are more effective for specific AML subtypes, challenging the traditional '3+7' chemotherapy approach.

While lower intensity therapies show high response rates, they are less effective at preventing relapses, and the only curative option for poor-risk AML remains allogeneic stem cell transplant, indicating that '3+7' still plays a crucial role in combination therapies for suitable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3+7 Combined Chemotherapy for Acute Myeloid Leukemia: Is It Time to Say Goodbye? Tang, K., Schuh, AC., Yee, KW.[2022]

Citations

1. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-japanese-approval-pemazyrer-pemigatinib

Incyte Announces Japanese Approval of Pemazyre® ... The primary endpoint, investigator-assessed complete response rate, was 62.5% (95% CI: 45.8 - 77.3). The complete response rate in the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36927350/

Pemigatinib for the treatment of myeloid/lymphoid ... High rates of complete hematologic and cytogenetic response have been observed. While direct comparative data are unavailable, outcomes appear favorable ...

3. incytemi.com incytemi.com/document/Poster/EHA%202024%20-%20FIGHT-203%20updated%20data%20(poster).pdf

A Phase 2 Study of Pemigatinib (FIGHT-203 *Three patients had treated MLN without BM/PB/EMD involvement but persistent 8p11 translocation and/or FGFR rearrangement; 3 patients had ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03011372

NCT03011372 | A Study to Evaluate the Efficacy and ... The purpose of this study is to evaluate the efficacy and safety of pemigatinib (INCB054828) in subjects with myeloid/lymphoid neoplasms with fibroblast growth ...

5. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-pemazyrer-pemigatinib-first-and

Incyte Announces FDA Approval of Pemazyre® ... Pemazyre, a fibroblast growth factor receptor (FGFR) inhibitor, is the first targeted treatment approved for use in the United States for ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213736Orig1s000MultidisciplineR.pdf

213736Orig1s000 - accessdata.fda.gov • The primary data supporting the safety of pemigatinib for the ... myeloid leukemia; ARF=acute renal failure; BUN=blood urea nitrogen;.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10618723/

A Year of Advances in Precision Therapy for Blood Cancers Recent advances in precision therapies of blood cancers are highlighted here, adapted from the 13th edition of the annual AACR Cancer Progress Report.