JNJ-75276617 Combination Therapy for Acute Myeloid Leukemia

Recruiting at 46 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Acute promyelocytic leukemia, Down syndrome, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called bleximenib (also known as JNJ-75276617) for people with acute myeloid leukemia (AML), a type of blood cancer. The study aims to determine the best dose of bleximenib when combined with other AML therapies and to assess its safety and tolerability. Researchers divide participants into groups based on specific genetic mutations and treatment histories. This trial suits those with AML who have certain genetic alterations and might not qualify for intense chemotherapy due to other health conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that bleximenib, a drug targeting a specific cellular interaction, may be promising when combined with other treatments for acute myeloid leukemia (AML). Early lab studies have demonstrated potential benefits for AML, but researchers are still gathering safety information in humans. This trial is in its early stages, focusing on determining safe dosage levels and monitoring for side effects. As a Phase 1 trial, it builds on earlier research that showed promise, but researchers are still assessing its safety in humans. Participants will help researchers understand how well people tolerate the treatment and identify any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about bleximenib for acute myeloid leukemia (AML) because it offers a new approach to tackling this challenging condition. Unlike standard treatments like chemotherapy, which broadly attack rapidly dividing cells, bleximenib is designed to target specific genetic alterations found in AML, such as KMT2A, NPM1, NUP98, and NUP214. This targeted action could potentially lead to more effective treatments with fewer side effects. Additionally, bleximenib can be combined with existing drugs like venetoclax and azacitidine, potentially enhancing their efficacy and offering new hope to patients who are newly diagnosed or have relapsed.

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

Research has shown that bleximenib holds promise for treating acute myeloid leukemia (AML). In studies, 82% of patients with AML that recurred or did not respond to other treatments experienced improvement when they took bleximenib with other therapies. This trial will evaluate bleximenib in different settings:

- In Arm A, participants with relapsed/refractory AML will receive bleximenib combined with either venetoclax (VEN), azacitidine (AZA), or both.

- In Arm B, newly diagnosed participants ineligible for intensive chemotherapy will receive bleximenib with VEN and AZA.

- In Arm C, newly diagnosed participants eligible for intensive chemotherapy will receive bleximenib with cytarabine and either daunorubicin or idarubicin.

Bleximenib targets a specific cellular process that can help stop cancer growth. Early lab tests showed that bleximenib reduced cancer cells and improved survival in AML models. These findings suggest that bleximenib could be an effective option for people with certain genetic changes in their AML. ^{1 3 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with Acute Myeloid Leukemia (AML) as per WHO criteria, including those with de novo or secondary AML and relapsed/refractory cases. Participants must be in relatively good health (ECOG grade 0-2), have adequate organ function, not require supplemental oxygen, and women of childbearing potential must test negative for pregnancy.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

Willing and able to adhere to the prohibitions and restrictions specified in this protocol

A woman of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment

Exclusion Criteria

I have received a solid organ transplant.

I need extra oxygen to help me breathe properly.

I have been diagnosed with a specific type of leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection

Participants receive bleximenib in combination with AML-directed therapies to determine the recommended Phase 2 dose (RP2D)

Up to 3 years 3 months

Dose Expansion

Participants receive bleximenib in combination with AML-directed therapies at the RP2D to evaluate safety and tolerability

Up to 3 years 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• JNJ-75276617

Trial Overview

The study tests JNJ-75276617 combined with other AML therapies like Venetoclax, Azacitidine, Cytarabine, Daunorubicin or Idarubicin to find the safest and most effective dose. It aims to establish a recommended Phase 2 dose and assess safety at that level.

How Is the Trial Designed?

Group I: Arm C: Newly Diagnosed Chemotherapy Eligible Setting Experimental Treatment 3 Interventions

Participants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants \>= 18 to \<75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy.

Group II: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting Experimental Treatment 3 Interventions

Participants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are \>=75 years of age or \>=18 years of age to \<75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.

Group III: Arm A: Relapsed/Refractory Setting Experimental Treatment 3 Interventions

Participants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (\>=) 12 years and less than (\<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s).

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In 2017, the FDA approved five new drugs for treating acute myeloid leukemia (AML), including targeted therapies for specific genetic mutations (FLT3 and IDH2) and a new formulation of cytarabine-daunorubicin for certain types of AML.

The combination of the BCL-2 inhibitor venetoclax with low-intensity therapy showed promising results for older patients who are not suitable for intensive chemotherapy, indicating a shift towards more tailored treatment options in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Wei, AH., Tiong, IS.[2022]

Recent advancements in the treatment of acute myeloid leukemia (AML) include new targeted therapies like CPX-351 and gemtuzumab ozogamicin, which have improved outcomes for specific patient subgroups.

The combination of midostaurin with intensive chemotherapy for FLT3-mutated AML and the use of IDH inhibitors (enasidenib and ivosidenib) have shown significant efficacy, particularly in relapsed cases, highlighting the potential of targeted therapies in AML management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Treatment Options for Acute Myeloid Leukemia in 2019. Cerrano, M., Itzykson, R.[2020]

Two investigational menin inhibitors, SNDX-5613 and KO-539, showed promising efficacy in treating relapsed and refractory acute myeloid leukemia (AML), with overall response rates of 53% and 40%, respectively, in patients with specific genetic mutations.

The combination of pivekimab sunirine with azacitidine and venetoclax achieved a 45% overall response rate in relapsed and refractory AML, which increased to 53% in patients who had not previously received venetoclax, highlighting the potential of novel treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents and regimens in acute myeloid leukemia: latest updates from 2022 ASH Annual Meeting. DiNardo, KW., LeBlanc, TW., Chen, H.[2023]

A patient with FLT3 positive acute myeloid leukemia achieved complete clinical and molecular remission after adding sorafenib to their chemotherapy regimen, indicating its efficacy in this context.

The combination treatment was well-tolerated, with only mild side effects reported, suggesting that sorafenib can be safely integrated into standard chemotherapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sorafenib in combination with chemotherapy in the induction therapy for FLT3-ITD positive acute monocytic leukemia: a case report and literature review]. Wei, SN., Wei, H., Mi, YC., et al.[2018]

The combination of vosaroxin and venetoclax synergistically induces apoptosis in acute myeloid leukemia (AML) cell lines and primary patient samples, suggesting a potent anti-leukemic effect.

This combination treatment effectively targets AML progenitor cells while sparing normal hematopoietic progenitor cells, indicating a potentially safer therapeutic option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. Liu, F., Knight, T., Su, Y., et al.[2020]

Citations

1.

jnj.com

jnj.com/media-center/press-releases/new-results-for-johnson-johnsons-bleximenib-demonstrate-promising-antileukemic-activity-in-combination-with-venetoclax-and-azacitidine-for-acute-myeloid-leukemia

New results for Johnson & Johnson's bleximenib ...

At the recommended Phase 2 dose (RP2D), patients with relapsed or refractory AML achieved an overall response rate (ORR) of 82 percent and a ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39704147/

Bleximenib, the novel menin-KMT2A inhibitor JNJ ...

Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.

3.

ashpublications.org

ashpublications.org/blood/article/144/11/1206/516663/Preclinical-efficacy-of-the-potent-selective-menin

Preclinical efficacy of the potent, selective menin-KMT2A ...

In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied ...

4.

haematologica.org

haematologica.org/article/view/11876

Bleximenib, the novel menin-KMT2A inhibitor JNJ ...

The novel inhibitor JNJ-75276617 (bleximenib) targets the menin-KMT2A interaction and has shown preclinical efficacy in AML.

5.

prnewswire.com

prnewswire.com/news-releases/new-results-for-johnson--johnsons-bleximenib-demonstrate-promising-antileukemic-activity-in-combination-with-venetoclax-and-azacitidine-for-acute-myeloid-leukemia-302480190.html

New results for Johnson & Johnson's bleximenib ...

At the recommended Phase 2 dose (RP2D), patients with relapsed or refractory AML achieved an overall response rate (ORR) of 82 percent and a ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12130779/

Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617 ...

The novel inhibitor JNJ-75276617 (bleximenib) targets the menin-KMT2A interaction and has shown preclinical efficacy in AML.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05453903

NCT05453903 | A Study of Bleximenib in Combination ...

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies.