What side effects are associated with this type of intervention?

Common treatments for Acute Leukemia, such as ivosidenib combined with azacitidine, venetoclax, and other chemotherapeutic agents, often have side effects including hematologic adverse events like neutropenia, anemia, and thrombocytopenia. Other notable side effects can include QT prolongation, differentiation syndrome, serious infections, hypersensitivity reactions, and prolonged cytopenias. These treatments aim to balance efficacy with manageable toxicity to improve patient outcomes.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Leukemia, including hypomethylating agents like azacitidine and decitabine, which are used for maintenance therapy. Oral azacitidine (CC-486) is approved for continued treatment of AML in patients unable to complete intensive curative therapy. IDH inhibitors and gemtuzumab ozogamicin are also approved for maintenance therapy. While decitabine is approved by the EMA for AML, it is not FDA-approved. These treatments aim to prolong remission and improve survival rates in acute leukemia patients.

What other types of research exist?

One promising alternative is DAB486IL-2, a recombinant fusion toxin that has shown significant activity in patients with chemotherapy refractory hematological cancers, including those expressing the p55 component of the IL-2 receptor. Another potential option is MK0974, a CGRP receptor antagonist that induces apoptosis in AML cell lines by disrupting ERK signaling. Both of these agents are in various stages of clinical evaluation and could be considered for treatment in 2024.

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CAR T-cell Therapy

JNJ-75276617 for Acute Leukemia

Q: What is the mechanism of action of this treatment?

The most common treatments for Acute Leukemia include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by using cytotoxic agents to kill rapidly dividing leukemia cells, but it also affects normal cells, leading to significant side effects. Targeted therapies, such as tyrosine kinase inhibitors, specifically inhibit abnormal proteins or pathways that drive leukemia cell growth, offering a more precise treatment with potentially fewer side effects. Immunotherapy leverages the patient's immune system to recognize and destroy leukemia cells, providing a novel approach that can be effective even in resistant cases. Understanding these mechanisms is crucial for patients as it helps in selecting the most appropriate treatment based on the specific characteristics of their leukemia, potentially improving outcomes and minimizing adverse effects.

Phase 1 & 2

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2

Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A) or nucleophosmin 1 gene (NPM1) alterations

Must not have

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)

Acute promyelocytic leukemia according to World Health Organization (WHO) 2016 criteria

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years and 9 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests JNJ-75276617, an oral drug designed to block a protein interaction that helps leukemia cells grow. It targets patients with specific genetic types of AML or ALL. By stopping these proteins from working together, the drug aims to slow down or stop cancer cell growth.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

While the side effects of JNJ-75276617 are being studied, potential risks may include reactions at the infusion site, changes in blood counts, liver issues, fatigue, nausea, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My acute leukemia has specific genetic changes.

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My acute leukemia has returned or is not responding to treatment, and I have no other treatment options.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with a specific type of leukemia.

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

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I have an active brain or spinal cord disease.

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I have had a solid organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years and 9 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years and 9 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years and 9 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Number of Participants with AEs by Severity

Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)

+1 more

Secondary study objectives

Phase 1 and 2: Duration of Response (DOR)

Phase 1 and 2: Overall Response Rate (ORR)

Phase 1 and 2: Time To Response (TTR)

+12 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: BleximenibExperimental Treatment1 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. Food effect cohort (optional) participants will receive bleximenib orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition. Participants in Phase 2 part of the study will receive bleximenib orally at the RP2D level(s).

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Leukemia include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by using cytotoxic agents to kill rapidly dividing leukemia cells, but it also affects normal cells, leading to significant side effects. Targeted therapies, such as tyrosine kinase inhibitors, specifically inhibit abnormal proteins or pathways that drive leukemia cell growth, offering a more precise treatment with potentially fewer side effects. Immunotherapy leverages the patient's immune system to recognize and destroy leukemia cells, providing a novel approach that can be effective even in resistant cases. Understanding these mechanisms is crucial for patients as it helps in selecting the most appropriate treatment based on the specific characteristics of their leukemia, potentially improving outcomes and minimizing adverse effects.

Immunotherapy in AML: a brief review on emerging strategies.Epigenetic deregulation in myeloid malignancies.Development of Personalized Molecular Therapy for Acute Myeloid Leukemia.