What side effects are associated with this type of intervention?

Common treatments for acute leukemia, particularly those involving targeted therapies like JNJ-75276617 combined with conventional chemotherapy, often include agents such as azacitidine, decitabine, and cytarabine. Known side effects of these treatments can include myelosuppression (leading to anemia, neutropenia, and thrombocytopenia), gastrointestinal symptoms (nausea, vomiting, diarrhea), infections due to immunosuppression, fatigue, and mucositis. Targeted therapies may also cause specific adverse effects related to the inhibition of their molecular targets, such as liver toxicity, skin rashes, and potential cardiovascular issues.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of acute leukemia, particularly those targeting specific genetic alterations. For instance, Decitabine, a hypomethylating agent, is approved for the treatment of acute myeloid leukemia (AML) by the European Medicines Agency (EMA) but not by the FDA. Venetoclax, often combined with hypomethylating agents like Decitabine or Azacitidine, has shown efficacy in AML, especially in patients with specific genetic mutations such as TP53. Additionally, the FDA has approved oral Azacitidine (CC-486) for post-remission maintenance therapy in AML. These treatments are somewhat similar to the targeted approach of JNJ-75276617, which focuses on genetic alterations like KMT2A1, NPM1, or nucleoporin alterations in relapsed/refractory acute leukemia.

What other types of research exist?

Promising novel alternatives to JNJ-75276617 for acute leukemia patients include: 1) Venetoclax, a BCL2 inhibitor, often combined with low-dose cytarabine or hypomethylating agents like azacitidine or decitabine. 2) FLT3 inhibitors such as gilteritinib for patients with FLT3 mutations. 3) IDH inhibitors like ivosidenib and enasidenib for patients with IDH1 and IDH2 mutations, respectively. 4) CAR-T cell therapies targeting specific antigens on leukemia cells. These alternatives have shown efficacy in clinical trials and are considered promising for the treatment of acute leukemia.

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Monoclonal Antibodies

JNJ-75276617 + Chemotherapy for Acute Leukemia

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

Common treatments for acute leukemia include intensive combination chemotherapy, targeted therapies, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, including cancer cells, but also affects normal cells, leading to significant side effects. Targeted therapies, such as those being studied in the JNJ-75276617 trial, focus on specific genetic alterations in leukemia cells, like KMT2A1, NPM1, or nucleoporin alterations, and aim to inhibit the pathways that drive cancer growth. This precision reduces damage to normal cells and potentially improves treatment efficacy and tolerability. Immunotherapy leverages the body's immune system to recognize and destroy cancer cells. These treatments are crucial for acute leukemia patients as they offer the potential for more effective and less toxic treatment options, improving survival rates and quality of life.

Phase 1

Waitlist Available

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 younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years 5 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, JNJ-75276617, combined with standard chemotherapy in children and young adults with hard-to-treat leukemia that has specific genetic changes. The drug works by blocking genes that help cancer cells grow, making chemotherapy more effective.

Who is the study for?

This trial is for young people with relapsed/refractory acute leukemia who have specific genetic changes (KMT2A, NPM1, or nucleoporin). They must be fairly active and have good kidney function. It's not for those with certain bone marrow syndromes, recent transplants, prior menin-KMT2A inhibitor treatment, uncontrolled graft-versus-host disease, Down syndrome associated leukemia or recent immunotherapy.

What is being tested?

The study tests JNJ-75276617 combined with standard chemotherapy to find the safest dose in kids and young adults with specific genetic types of acute leukemia. Part 1 figures out the right doses; Part 2 checks safety at these doses and also looks at JNJ-75276617 alone in some cases.

What are the potential side effects?

Possible side effects include reactions related to JNJ-75276617 and common chemo effects like nausea, hair loss, fatigue, increased infection risk due to low blood cell counts, mouth sores and potential organ damage.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years 5 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years 5 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years 5 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 AEs by Severity

Number of Participants with Adverse Events (AEs)

Number of Participants with Dose-Limiting Toxicity (DLT)

Secondary study objectives

Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation

Duration of Response (DOR)

Number of Participants with Depletion of Leukemic Blasts

+6 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: >=2 Years OldExperimental Treatment7 Interventions

Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617.

Group II: Arm A: <2 Years OldExperimental Treatment7 Interventions

Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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) has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fludarabine

2012

Completed Phase 4

~1860

Cytarabine

2016

Completed Phase 3

~3330

Intrathecal Chemotherapy

2020

Completed Phase 2

~40

Dexamethasone

2007

Completed Phase 4

~2650

Vincristine

2003

Completed Phase 4

~2970

Pegaspargase

2005

Completed Phase 3

~9260

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

Common treatments for acute leukemia include intensive combination chemotherapy, targeted therapies, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, including cancer cells, but also affects normal cells, leading to significant side effects. Targeted therapies, such as those being studied in the JNJ-75276617 trial, focus on specific genetic alterations in leukemia cells, like KMT2A1, NPM1, or nucleoporin alterations, and aim to inhibit the pathways that drive cancer growth. This precision reduces damage to normal cells and potentially improves treatment efficacy and tolerability. Immunotherapy leverages the body's immune system to recognize and destroy cancer cells. These treatments are crucial for acute leukemia patients as they offer the potential for more effective and less toxic treatment options, improving survival rates and quality of life.

Immunotherapy in AML: a brief review on emerging strategies.Epigenetic deregulation in myeloid malignancies.Acute myeloid leukemia.