JNJ-75276617 for Acute Leukemia

(cAMeLot-1 Trial)

Recruiting at 121 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Immunotherapy, Blinatumomab

Disqualifiers: Down syndrome leukemia, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

400 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 individuals with specific types of acute leukemia, a cancer of the blood and bone marrow. The research aims to determine the optimal dose of bleximenib that is both safe and effective in slowing or stopping leukemia. Participants will receive the treatment in different phases to evaluate its efficacy and safety. This trial may suit those with relapsed or resistant acute leukemia who have specific genetic changes, such as KMT2A or NPM1 mutations, and have not succeeded with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had prior cancer immunotherapy within 4 weeks before joining the trial, and other cancer therapies must not be given within 4 weeks or 5 half-lives of the agent, whichever is shorter.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that JNJ-75276617, also known as bleximenib, has been safe in previous studies. Earlier research found no serious heart rhythm problems and no severe side effects. Only a few mild side effects were reported, which encourages those considering participation. Overall, the safety data suggest that bleximenib is well-tolerated, making it a good option for participants in this study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and targeted therapies for acute leukemia, bleximenib is unique because it targets specific proteins involved in the growth and survival of leukemia cells. Researchers are excited about bleximenib because it offers a novel mechanism of action that could potentially overcome resistance seen with current treatments. Additionally, bleximenib is administered orally, providing a more convenient option compared to traditional intravenous therapies. These features make bleximenib a promising candidate for improving outcomes in acute leukemia patients.

What evidence suggests that JNJ-75276617 might be an effective treatment for acute leukemia?

Research has shown that bleximenib, the investigational treatment in this trial, yields promising results for acute leukemia. In one study, 82% of patients with relapsed or hard-to-treat acute myeloid leukemia (AML) improved with the recommended dose of bleximenib, indicating that most patients experienced better outcomes. Earlier animal studies also support these findings, demonstrating that bleximenib reduced leukemia and extended survival. These results suggest that bleximenib may work by targeting a specific protein interaction in cancer cells. ^{1 2 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 leukemia who have specific genetic alterations (KMT2A or NPM1), and whose disease has not improved after treatment, or they can't receive standard treatments. They must be in relatively good health otherwise, with acceptable blood counts and organ function. Women of childbearing age and men must agree to use contraception.

Inclusion Criteria

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

I agree to use a condom and not donate sperm during and 90 days after the study.

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

Exclusion Criteria

I have been diagnosed with a specific type of leukemia.

My heart's electrical cycle length is within safe limits and I don't have a family history of Long QT syndrome.

Exclusion criteria related to stem cell transplant: a. Willing and able to undergo allogeneic stem cell transplant (if clinically indicated); b. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; c. Has evidence of graft versus host disease; d. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; e. Requires immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive bleximenib orally with dose levels escalated based on dose limiting toxicities evaluation

Up to 28 days

Dose Expansion

Participants receive bleximenib orally at the recommended Phase 2 dose(s) determined in Dose Escalation

Up to 4 years and 9 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 is testing JNJ-75276617 to find the safest dose that's also effective (Phase 2). It starts by increasing doses (Part 1) then tests this dose further for safety and effectiveness (Part 2).

How Is the Trial Designed?

Group I: Bleximenib Experimental Treatment 1 Intervention

Participants in Phase 1 Part 1 (dose escalation) will receive bleximenib orally. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) have been identified. Participants in Phase 1 Part 2 (dose expansion) will receive bleximenib orally at the RP2D(s) determined in Part 1. In Phase 2 participants will receive bleximenib at the RP2D to evaluate anti-leukemia activity and demonstrate acceptable safety 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

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. 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 ...

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

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.

4. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper172422.html

57 A First-in-Human Phase 1 Study of the Menin-KMT2A ... Results: Fifty-eight pts received JNJ-75276617. The median age was 63 (range: 19-83) years; 56 pts (97%) had R/R AML and 2 (3%) had ...

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 ... Our data indicate that JNJ-75276617 provides a potential therapeutic approach whereby not only proliferation is impaired and differentiation is induced, but ...

7. jnjmedicalconnect.com jnjmedicalconnect.com/media/attestation/congresses/oncology/2024/ash/bleximenib-dose-optimization-and-determination-of-rp2d-from-a-phase-1-study-in-relapsedrefractory-ac.pdf

bleximenib-dose-optimization-and-determination-of-rp2d- ... Bleximenib Menin Inhibitor Monotherapy (cAMeLot-1) in R/R Acute Leukemia. Background. • R/R altered acute leukemias have poor outcomes, with ...