What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include cytotoxic chemotherapy agents such as cytarabine, daunorubicin, and idarubicin, which often cause side effects like cytopenias, febrile neutropenia, and infections. Hypomethylating agents like azacitidine and decitabine can lead to similar toxicities, including cytopenias and neutropenic fever. Newer targeted therapies and antibody-drug conjugates, which may be similar to JNJ-74856665, can also cause significant hematologic toxicities, including cytopenias and increased risk of infections. Monitoring and supportive care are essential to manage these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML). Hypomethylating agents such as azacitidine and decitabine are commonly used, with azacitidine available in both parenteral and oral forms (CC-486). IDH inhibitors like ivosidenib (IDH1) and enasidenib (IDH2) are also approved for specific genetic mutations. Additionally, venetoclax in combination with azacitidine or decitabine is approved for newly diagnosed AML in patients ineligible for intensive chemotherapy. Gemtuzumab ozogamicin is another option for maintenance therapy. These treatments aim to manage AML by targeting various pathways involved in the disease's progression.

What other types of research exist?

Promising novel alternatives to JNJ-74856665 for AML patients include JNJ-67571244, a CD33xCD3 bispecific antibody that redirects T-cells to target CD33-expressing AML cells, and venetoclax, a BCL2 inhibitor used in combination with low-dose cytarabine (LoDAC) for initial treatment. Both have shown significant antitumor activity and efficacy in clinical settings.

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JNJ-74856665 for AML and MDS (DHODH Trial)

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

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

A diagnosis of: Arms A and C: Acute Myeloid Leukemia (AML) according to the World Health Organization (WHO) 2016 criteria with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; or newly transformed secondary AML according to the WHO 2016 criteria and have exhausted standard therapeutic options for AML during their treatment prior to transformation; or high-risk or very high-risk Myelodysplastic Syndrome (MDS) according to the WHO 2016 criteria and the revised International Prognostic Scoring System (IPSS-R) with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; or Arm A only: chronic myelomonocytic leukemia-2 (CMML-2) according to the WHO 2016 criteria with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; Arm B: Eligible participants must be considered unsuitable for intensive treatment with a curative intent (including stem cell transplantation), but eligible to receive Azacitidine (AZA) treatment with the following underlying diseases: AML (newly diagnosed or relapsed/refractory) according to the 2016 WHO classification only if Venetoclax (VEN) + hypomethylating agent (HMA) (or low-dose cytarabine) is not indicated or available; or high-risk or very high-risk MDS according to the 2016 WHO classification and IPSS-R; or CMML-2 according to the WHO 2016 criteria; Arm D: Very low, low, or intermediate-risk MDS according to the 2016 WHO classification and IPSS-R and the following: Transfusion dependence defined as requiring at least 3 red blood cell (RBC) units transfused within 16 weeks prior to C1D1; pre-transfusion hemoglobin (Hb) should be less than (<) 9.0 grams per decilitre (g/dL) to count towards the 3 units total, Relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment or endogenous serum erythropoietin (EPO) level greater than (>) 500 milliunits per milliliter (mU/mL). Exception: Del(5q) karyotype is allowed, provided prior treatment with lenalidomide has failed or participant was ineligible to receive lenalidomide

Must not have

Known allergies, hypersensitivity, or intolerance to JNJ-74856665, AZA, or VEN or the excipients of these treatments

Acute promyelocytic leukemia according to World Health Organization 2016 criteria

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years and 10 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called JNJ-74856665, alone or with other drugs, in patients with specific blood cancers like AML, MDS, and CMML. The goal is to see if it can safely stop cancer cells from growing and make them die.

Who is the study for?

This trial is for adults with certain blood disorders like AML or MDS who've tried other treatments without success, or can't use them. It's also for those unsuitable for intensive treatment but can take AZA, and some with lower-risk MDS needing regular blood transfusions. Participants must be in good physical condition and women/men agree to contraception.

What is being tested?

The study tests JNJ-74856665 alone or combined with AZA (Azacitidine) or VEN (Venetoclax), aiming to find the safest doses. The focus is on how well patients tolerate these drugs and what effects they have on their diseases.

What are the potential side effects?

Possible side effects include reactions related to the immune system, digestive issues, fatigue, changes in blood counts which could increase infection risk, and potential organ inflammation. Specific side effects will depend on individual patient responses.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or restricted in physically strenuous activity but can do light work.

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You have been diagnosed with certain types of blood cancers or disorders and have exhausted or are not eligible for standard treatment options. This includes acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia-2 (CMML-2). In some cases, you may be eligible if you are not suitable for intensive treatment or stem cell transplantation.

Exclusion Criteria

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

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I am allergic to JNJ-74856665, AZA, VEN, or their ingredients.

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I have been diagnosed with a specific type of leukemia.

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My cancer has spread to my brain or spinal cord.

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I have been treated with or cannot tolerate a DHODH inhibitor for cancer or other reasons.

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Side effects from my previous cancer treatments, except for hair loss, nerve issues, low platelet count, low white blood cell count, or anemia, have mostly gone away.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years and 10 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years and 10 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years and 10 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

Arms A and D: Number of Participants with Dose-Limiting Toxicity (DLT)

Arms A, B, C and D: Number of Participants with AEs by Severity

Arms A, B, C and D: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

+1 more

Secondary study objectives

Arm A, Arm B and Arm C: Clinical Response of all Participants with a Primary Disease of Acute Myeloid Leukemia (AML)

Muscular Dystrophy

Arm A, Arm B and Arm C: Clinical Response of all Participants with a Primary Disease of chronic myelomonocytic leukemia-2 (CMML-2)

+7 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm D: JNJ-74856665Experimental Treatment1 Intervention

Participants will receive JNJ-74856665 orally in a 21-day cycle. Participants with transfusion dependent relapsed/refractory Myelodysplastic Syndrome (MDS) will be included.

Group II: Arm C: JNJ-74856665 + Venetoclax (VEN)Experimental Treatment2 Interventions

Participants will receive JNJ-74856665 orally in combination with VEN in a 28-day cycle.

Group III: Arm B: JNJ-74856665 + Azacitidine (AZA)Experimental Treatment2 Interventions

Participants will receive JNJ-74856665 orally in combination with AZA administered intravenously (IV) or subcutaneously (SC) in a 28-day cycle.

Group IV: Arm A: JNJ-74856665Experimental Treatment1 Intervention

Participants will receive JNJ-74856665 orally in a 21-day cycle. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until a recommended Phase 2 dose (RP2D) has been identified.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AZA

2016

Completed Phase 3

~180

0 / 7Eligibility 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

Common treatments for Acute Myeloid Leukemia (AML) include targeted therapies and chemotherapeutic agents. Clofarabine, a chemotherapeutic agent, works by inhibiting DNA synthesis, leading to cell death, but it can cause significant myelosuppression and toxicity. Gilteritinib, a targeted therapy, inhibits the FLT3 receptor tyrosine kinase, which is often mutated in AML, thereby blocking the signaling pathways that promote leukemic cell proliferation. The use of growth factors like G-CSF and GM-CSF aims to reduce treatment toxicity and cytopenia duration, although their role is controversial due to potential leukemogenic effects. Understanding these mechanisms is crucial for AML patients as it helps in selecting appropriate treatments that target specific pathways involved in their disease, potentially improving outcomes and minimizing adverse effects.

Epigenetic deregulation in myeloid malignancies.Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors.FLT3 inhibitors in the treatment of acute myeloid leukemia: current status and future perspectives.