What side effects are associated with this type of intervention?

Common treatments for AML that are similar to JNJ-75276617 include IDH inhibitors like ivosidenib and enasidenib. Ivosidenib can cause differentiation syndrome (DS), prolonged QTc interval, fatigue, and rare cases of posterior reversible encephalopathy syndrome (PRES) and Guillain-Barré syndrome. Enasidenib's side effects include diarrhea, nausea, and DS. Both drugs require careful monitoring due to the potential severity of these adverse effects.

What prior FDA approvals exist?

Several targeted therapies and small molecule inhibitors have been approved by the FDA for the treatment of Acute Myeloid Leukemia (AML). Venetoclax, a BCL-2 inhibitor, is approved for use in combination with hypomethylating agents (HMAs) like azacitidine or decitabine for newly diagnosed AML in patients who are ineligible for intensive chemotherapy. Ivosidenib, an IDH1 inhibitor, is approved for the treatment of AML with a susceptible IDH1 mutation. Gilteritinib, an FLT3 inhibitor, is approved for the treatment of relapsed or refractory AML with an FLT3 mutation. These approvals highlight the FDA's recognition of the importance of targeted therapies in improving outcomes for AML patients.

What other types of research exist?

Promising novel alternatives to JNJ-75276617 for AML patients include venetoclax, ivosidenib, and gilteritinib. Venetoclax, when combined with hypomethylating agents (HMAs) like azacitidine or decitabine, has shown improved outcomes. Ivosidenib, an IDH1 inhibitor, is effective for patients with IDH1 mutations. Gilteritinib, an FLT3 inhibitor, has demonstrated efficacy in combination with azacitidine for patients with FLT3 mutations.

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CAR T-cell Therapy

JNJ-75276617 Combination Therapy for Acute Myeloid Leukemia

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

The most common treatments for Acute Myeloid Leukemia (AML) include targeted therapies and small molecule inhibitors, which work by specifically targeting and inhibiting the molecular abnormalities driving the cancer. For example, FLT3 inhibitors target mutations in the FLT3 gene, IDH inhibitors target mutations in the IDH1 or IDH2 genes, and hypomethylating agents like azacitidine and decitabine inhibit DNA methylation, leading to reactivation of tumor suppressor genes. These targeted approaches are crucial for AML patients as they offer more precise treatment options with potentially fewer side effects compared to traditional chemotherapy, and they can be particularly effective in patients with specific genetic mutations.

Phase 1

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

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years 3 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests JNJ-75276617, an oral drug that blocks a key protein interaction in leukemia cells. It targets adults with AML who have specific genetic changes making their disease hard to treat. The drug aims to stop cancer cells from growing and spreading.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical reactions associated with chemotherapy such as nausea, fatigue, increased risk of infection due to low blood cell counts; liver or kidney issues; bleeding problems; heart complications; allergic reactions to the drugs used.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years 3 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years 3 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years 3 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

Number of Participants with Adverse Events (AEs)

Number of Participants with Adverse Events (AEs) by Severity

Number of Participants with Dose-limiting Toxicity (DLT)

Secondary study objectives

Number of Participants with Depletion of Leukemic Blasts

Percentage of Participants who Achieve Complete Remission (CR)

Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C: Newly Diagnosed Chemotherapy Eligible SettingExperimental Treatment3 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 either NPM1 or KMT2A alterations and eligible for intensive chemotherapy.

Group II: Arm B: Newly Diagnosed Chemotherapy Ineligible SettingExperimental Treatment3 Interventions

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

Group III: Arm A: Relapsed/Refractory SettingExperimental Treatment3 Interventions

Participants with relapsed/refractory AML harboring either NPM1 or KMT2A 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) 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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine (AZA)

2012

Completed Phase 1

~10

Cytarabine

2016

Completed Phase 3

~3330

Do I qualify?Apply below to find out

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 Myeloid Leukemia (AML) include targeted therapies and small molecule inhibitors, which work by specifically targeting and inhibiting the molecular abnormalities driving the cancer. For example, FLT3 inhibitors target mutations in the FLT3 gene, IDH inhibitors target mutations in the IDH1 or IDH2 genes, and hypomethylating agents like azacitidine and decitabine inhibit DNA methylation, leading to reactivation of tumor suppressor genes. These targeted approaches are crucial for AML patients as they offer more precise treatment options with potentially fewer side effects compared to traditional chemotherapy, and they can be particularly effective in patients with specific genetic mutations.

Epigenetic deregulation in myeloid malignancies.Role of epigenetic in leukemia: From mechanism to therapy.Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia.

Find a Location

Who is running the clinical trial?

Janssen Research & Development, LLCLead Sponsor

1,003 Previous Clinical Trials

6,397,796 Total Patients Enrolled

Janssen Research & Development, LLC Clinical TrialStudy DirectorJanssen Research & Development, LLC

769 Previous Clinical Trials

3,973,536 Total Patients Enrolled

Media Library

JNJ-75276617 (CAR T-cell Therapy) Clinical Trial Eligibility Overview. Trial Name: NCT05453903 — Phase 1

$Acute Myeloid Leukemia Research Study Groups: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting, Arm A: Relapsed/Refractory Setting, Arm C: Newly Diagnosed Chemotherapy Eligible Setting$