#1 Clinical Trials Search in Europe

JNJ-75276617

A clinical trial is currently investigating JNJ-75276617, a promising new drug for pediatric and young adult patients with relapsed or refractory acute leukemias that have specific genetic alterations (KMT2A, NPM1, or nucleoporin). This Phase I/Ib study aims to determine the optimal dosage of JNJ-75276617 when combined with conventional chemotherapy. The trial focuses on patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and acute leukemia of ambiguous lineage who haven’t responded adequately to previous treatments. By testing different dosages and monitoring safety, researchers hope to find effective treatment options for these challenging cases of leukemia.

Table of Contents

What is JNJ-75276617?

JNJ-75276617 is an investigational drug being studied for the treatment of certain types of acute leukemia in children and young adults[1]. This medication is specifically designed to target leukemias with specific genetic alterations, including changes in genes called KMT2A (also known as MLL), NPM1, or nucleoporin genes. These genetic changes are known to play important roles in the development of certain types of leukemia.

The drug is currently being investigated in clinical trials and is not yet approved for general use. It represents a targeted approach to leukemia treatment, focusing on specific genetic features of cancer cells rather than attacking all rapidly dividing cells as traditional chemotherapy does[1].

What Types of Leukemia Does JNJ-75276617 Target?

JNJ-75276617 is being studied for several types of acute leukemia, including[1]:

  • Acute Myeloid Leukemia (AML) – A type of cancer that affects the bone marrow and blood, starting in cells that would normally develop into different types of blood cells
  • Acute Lymphoblastic Leukemia (ALL) – A cancer of the blood and bone marrow that affects white blood cells called lymphocytes
  • Acute Leukemia of Ambiguous Lineage – A rare type of leukemia that shows features of both myeloid and lymphoid cells, making it difficult to classify

Importantly, the drug specifically targets leukemias that have alterations in certain genes, including KMT2A, NPM1, or nucleoporin genes. These genetic changes can drive the development and growth of leukemia cells[1].

How Does JNJ-75276617 Work?

JNJ-75276617 appears to work by targeting the interaction between a protein called menin and the KMT2A (also known as MLL) protein[1]. In certain types of leukemia, this interaction contributes to the growth and survival of cancer cells.

The medication is designed to disrupt this interaction, which may lead to[1]:

  • Depletion of leukemic blasts – Reduction in the number of immature cancer cells
  • Differentiation of leukemic blasts – Helping cancer cells to mature into normal blood cells
  • Changes in expression of KMT2A target genes – Altering the activity of genes that are controlled by the KMT2A protein

By targeting these specific molecular mechanisms, JNJ-75276617 represents a more precise approach to treating leukemia compared to conventional chemotherapy[1].

Current Clinical Trial Information

JNJ-75276617 is currently being studied in a Phase I/Ib clinical trial for pediatric and young adult patients with relapsed or refractory acute leukemia[1]. “Relapsed” means the leukemia has returned after initial treatment, while “refractory” means the cancer hasn’t responded adequately to previous treatments.

The study has two main parts[1]:

  1. Dose Escalation (Part 1): To determine the recommended Phase 2 dose(s) of JNJ-75276617 when used in combination with conventional chemotherapy
  2. Dose Expansion (Part 2): To further evaluate the safety of JNJ-75276617 at the recommended dose, both in combination with chemotherapy and as a standalone treatment in select patients with a low burden of disease

The trial includes two age groups[1]:

  • Arm A: Patients less than 2 years old
  • Arm B: Patients 2 years and older

The starting doses are based on previous adult studies, with adjustments made according to age[1].

How JNJ-75276617 is Administered

JNJ-75276617 is administered orally (taken by mouth) on a 28-day cycle[1]. This makes it more convenient than medications that must be given by injection or intravenous infusion.

The exact dosage depends on several factors, including[1]:

  • The patient’s age
  • How well the medication is tolerated
  • Results from ongoing assessments during the trial

Researchers are carefully evaluating different dose levels to find the optimal amount that provides therapeutic benefit while minimizing side effects[1].

Combination Therapy Approach

In the clinical trial, JNJ-75276617 is being used in combination with conventional chemotherapy drugs, which differs based on the type of leukemia[1]:

For patients with Acute Myeloid Leukemia (AML), the combination includes[1]:

  • Fludarabine – Given as an intravenous (IV) infusion
  • Cytarabine – Given as an IV infusion
  • Intrathecal chemotherapy – Medication delivered directly to the fluid surrounding the brain and spinal cord

For patients with B-cell Acute Lymphoblastic Leukemia (ALL), the combination includes[1]:

  • Dexamethasone – A steroid medication given as an IV infusion
  • Vincristine – Given as an IV infusion
  • Pegaspargase – Given as an IV infusion
  • Intrathecal chemotherapy – As described above

Using JNJ-75276617 in combination with these established chemotherapy drugs may potentially enhance the overall effectiveness of treatment[1].

Expected Treatment Outcomes

While the clinical trial is still ongoing, researchers are measuring several outcomes to evaluate the effectiveness of JNJ-75276617[1]:

  • Overall Response Rate (ORR) – The percentage of patients whose cancer shrinks or disappears after treatment
  • Time to Response (TTR) – How quickly patients respond to the treatment
  • Duration of Response (DOR) – How long the response lasts before the cancer progresses again
  • Percentage of patients who can proceed to stem cell transplantation – An important goal for many patients with acute leukemia

For patients with AML, a complete response might include complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh)[1].

For patients with B-cell ALL, response is measured as complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)[1].

Safety Monitoring and Side Effects

As with any investigational treatment, monitoring for side effects is a crucial part of the JNJ-75276617 clinical trial[1]. Researchers are carefully tracking:

  • Adverse Events (AEs) – Any unfavorable and unintended signs, symptoms, or diseases that occur during the trial
  • Severity of AEs – Rated on a scale from Grade 1 (mild) to Grade 5 (death)
  • Dose-Limiting Toxicities (DLTs) – Specific side effects that may limit how much of the drug can be given safely

The trial includes a dedicated period (the first 28-day cycle) to specifically monitor for DLTs[1]. This helps researchers determine the maximum safe dose for future studies.

Since this is an early-phase trial, comprehensive information about all possible side effects is still being collected. Patients in the trial are closely monitored with regular medical assessments, blood tests, and other evaluations to ensure safety[1].

Study Aspect Details
Drug Name JNJ-75276617
Type of Study Phase I/Ib clinical trial
Target Population Pediatric and young adult patients with relapsed/refractory acute leukemias harboring KMT2A, NPM1, or nucleoporin gene alterations
Conditions Studied Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Acute Leukemia of Ambiguous Lineage
Study Design Two parts: Dose Escalation (Part 1) and Dose Expansion (Part 2)
Age Groups Two arms: <2 years old and ≥2 years old
Administration JNJ-75276617 given orally; conventional chemotherapy drugs administered intravenously
Combination Therapies For AML: Fludarabine, Cytarabine, Intrathecal Chemotherapy
For B-cell ALL: Dexamethasone, Vincristine, Pegaspargase, Intrathecal Chemotherapy
Primary Outcomes Safety assessment (adverse events and their severity), Dose-limiting toxicity
Secondary Outcomes Pharmacokinetics, Effects on leukemic blasts, Response rates, Time to response, Duration of response, Progression to stem cell transplantation
Follow-up Period Up to 3 years and 5 months

FAQ

  • What is JNJ-75276617 and how does it work? JNJ-75276617 is an investigational drug being studied for treating certain types of leukemia. It works by targeting specific genetic alterations (KMT2A, NPM1, or nucleoporin) found in some leukemia cells. The drug appears to affect the menin-KMT2A interaction, which plays a role in the development of certain leukemias. In the clinical trial, it's being tested both in combination with conventional chemotherapy and as a standalone treatment for specific patients.
  • Who is eligible for this clinical trial? This trial is designed for pediatric and young adult patients with relapsed or refractory acute leukemias (meaning their cancer has returned or didn't respond adequately to previous treatments). Specifically, patients must have acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia of ambiguous lineage. Additionally, their leukemia must have specific genetic alterations, namely KMT2A, NPM1, or nucleoporin gene alterations. The study includes patients of different age groups, with specific treatment arms for those under 2 years old and those 2 years and older.
  • How is the medication administered in this trial? In this trial, JNJ-75276617 is administered orally (by mouth) on a 28-day cycle. The conventional chemotherapy drugs that may be combined with JNJ-75276617 are administered differently: fludarabine, cytarabine, dexamethasone, vincristine, and pegaspargase are given as intravenous (IV) infusions. Intrathecal chemotherapy is also administered to participants with AML or B-cell ALL. The specific chemotherapy drugs used depend on the type of leukemia – patients with AML receive a different combination than those with B-cell ALL.
  • What are the main goals of this clinical trial? The primary goals of this trial are to determine the safety of JNJ-75276617 and identify the recommended Phase 2 dose (RP2D) when combined with conventional chemotherapy. Researchers are closely monitoring adverse events, their severity, and any dose-limiting toxicities. Secondary goals include measuring how the drug behaves in the body, observing its effects on leukemia cells (including depletion and differentiation of leukemic blasts), and evaluating treatment responses. The study will also track how many patients are able to proceed to stem cell transplantation after treatment with JNJ-75276617.
  • How long will participants be followed in this study? Participants in this clinical trial will be followed for up to 3 years and 5 months. During this time, researchers will monitor various outcomes including safety (adverse events), response to treatment, time to response, and duration of response. This extended follow-up period allows the research team to gather comprehensive data about both the short-term and longer-term effects of treatment with JNJ-75276617, either alone or in combination with conventional chemotherapy.

Ongoing Clinical Trials on JNJ-75276617

  • A Study Testing Bleximenib in People with Acute Leukemia

    Recruiting

    1 1
    Investigated drugs:
    Belgium France The Netherlands Spain

  • Study of Bleximenib with Drug Combination for Patients with Acute Myeloid Leukemia with KMT2A or NPM1 Alterations

    Not recruiting

    1 1 1
    Investigated drugs:
    France Germany Italy Spain

Glossary

  • Acute Leukemia: A fast-progressing cancer of the blood and bone marrow that affects the development of blood cells. It's called 'acute' because it can progress quickly and create immature blood cells that cannot function properly.
  • Acute Myeloid Leukemia (AML): A type of cancer where the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. It progresses rapidly and requires prompt treatment.
  • Acute Lymphoblastic Leukemia (ALL): A type of cancer where the bone marrow makes too many immature lymphocytes (a type of white blood cell). It's the most common type of cancer in children but can also affect adults.
  • Acute Leukemia of Ambiguous Lineage: A rare type of leukemia that has characteristics of both myeloid and lymphoid leukemias, making it difficult to classify as either AML or ALL.
  • Relapsed/Refractory: Relapsed means the cancer has returned after a period of improvement. Refractory means the cancer has not responded to treatment. These conditions are typically more difficult to treat than newly diagnosed cases.
  • KMT2A Gene: Also known as MLL gene, this is a gene that, when altered, can contribute to the development of certain types of leukemia. KMT2A stands for histone-lysine N-methyltransferase 2A.
  • NPM1 Gene: Nucleophosmin 1 gene, which when mutated is associated with certain types of leukemia, particularly some forms of AML.
  • Nucleoporin: A family of proteins that make up the nuclear pore complex, which regulates the transport of substances between the cell nucleus and cytoplasm. Alterations in nucleoporin genes can be associated with certain leukemias.
  • Phase I/Ib Study: An early-stage clinical trial that focuses on determining the safety, side effects, and best dose of a new treatment. Phase Ib is an expansion of Phase I that may include more participants.
  • Recommended Phase 2 Dose (RP2D): The dose determined in a Phase I study that will be used in subsequent Phase II trials. It's typically the highest dose that doesn't cause unacceptable side effects.
  • Dose Escalation: A process in clinical trials where the dose of a drug is gradually increased to find the optimal balance between effectiveness and side effects.
  • Dose Expansion: A phase in clinical trials where more participants receive the treatment at the dose determined in the dose escalation phase, to gather more data on safety and effectiveness.
  • Dose-Limiting Toxicity (DLT): Side effects that are severe enough to prevent increasing the dose of a drug in a clinical trial.
  • Adverse Event (AE): Any undesirable experience associated with the use of a medical product in a patient. The event may or may not be related to the treatment.
  • Leukemic Blasts: Immature, abnormal white blood cells that multiply uncontrollably in leukemia. A high blast count indicates active disease.
  • Differentiation of Leukemic Blasts: The process by which immature leukemic cells develop into more mature cells. Promoting differentiation can be a therapeutic strategy in leukemia.
  • Overall Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Complete Response (CR): The disappearance of all signs of cancer in response to treatment.
  • Complete Response with incomplete hematologic recovery (CRi): A treatment response where the cancer appears to be gone, but blood cell counts have not returned completely to normal levels.
  • Complete Response with partial hematologic recovery (CRh): A treatment response where the cancer appears to be gone, and blood cell counts have partially, but not fully, recovered.
  • Time to Response (TTR): The time from the start of treatment until the cancer shows a response.
  • Duration of Response (DOR): The length of time from when the cancer responds to treatment until it starts growing again.
  • Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): A procedure where a patient receives blood-forming stem cells from a donor. It's often used after other treatments to help replace damaged bone marrow in leukemia patients.
  • Intrathecal Chemotherapy: A method of delivering chemotherapy directly into the cerebrospinal fluid that surrounds the brain and spinal cord, used to treat or prevent cancer spread to the central nervous system.
  • Intravenous (IV) Infusion: Administration of medications or fluids directly into a vein over a period of time.

References

  1. https://clinicaltrials.gov/study/NCT05521087