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4-{[(3S)-2-(4-Chloro-2-{4-[(5-Cyano-1,2-Dimethyl-1H-Pyrrol-3-Yl)(4-Hydroxyphenyl)Carbamoyl]-1,5-Dimethyl-1H-Pyrrol-2-Yl}Benzoyl)-1,2,3,4-Tetrahydroisoquinolin-3-Yl]Methyl}Morpholin-4-Ium Hydrogen Sulfate

This article discusses a clinical trial investigating the use of S65487, a Bcl2 inhibitor, in combination with azacitidine for treating adult patients with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive treatment. The study is designed in two phases: Phase I aims to determine the safety profile and optimal dosage, while Phase II will assess the efficacy of this combination therapy. This trial offers hope for AML patients who cannot undergo intensive chemotherapy due to age or other health conditions.

Table of Contents

What is S65487?

S65487 is a new drug being studied for the treatment of Acute Myeloid Leukemia (AML). It is classified as a Bcl-2 inhibitor, which means it targets a specific protein in cancer cells that helps them survive.[1] The full chemical name of S65487 is quite complex: 4-{[(3S)-2-(4-CHLORO-2-{4-[(5-CYANO-1,2-DIMETHYL-1H-PYRROL-3-YL)(4-HYDROXYPHENYL)CARBAMOYL]-1,5-DIMETHYL-1H-PYRROL-2-YL}BENZOYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-3-YL]METHYL}MORPHOLIN-4-IUM HYDROGEN SULFATE. However, for simplicity, it’s referred to as S65487 in clinical settings.

Target Condition: Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML) is a type of blood cancer that affects the bone marrow, where blood cells are made. In AML, the body produces too many immature white blood cells, which can crowd out healthy blood cells and lead to various health problems.[1] AML is a serious condition that often requires prompt treatment, especially in older adults or those with certain health conditions who may not be able to tolerate intensive chemotherapy.

Clinical Trial Overview

S65487 is currently being studied in a Phase I/II clinical trial. This trial is designed to test the safety and effectiveness of S65487 when combined with another drug called azacitidine in treating AML.[1] The trial is specifically for adult patients with previously untreated AML who are not eligible for intensive treatment, such as those aged 75 or older or those with certain health conditions.

How S65487 Works

S65487 is a Bcl-2 inhibitor. Bcl-2 is a protein that helps cancer cells survive by preventing them from undergoing a natural process of cell death called apoptosis. By inhibiting Bcl-2, S65487 aims to make cancer cells more vulnerable to destruction, potentially slowing or stopping the growth of leukemia.[1]

How S65487 is Administered

S65487 is given as a solution for intravenous infusion. This means it’s delivered directly into the bloodstream through a vein. The drug comes in a 100 mg solution form.[1] The exact dosing and schedule will be determined during the clinical trial.

Who is Eligible for the Trial?

The trial is open to adults aged 18 and older with confirmed AML who are not eligible for standard intensive chemotherapy. This includes:

  • Patients aged 75 or older
  • Patients 18 or older with specific health conditions, such as:
    • Significant heart or lung problems
    • Other conditions that make intensive chemotherapy unsuitable

Patients must also have adequate kidney and liver function and a white blood cell count below a certain level.[1]

Trial Objectives and Endpoints

The trial has several objectives:

  1. To determine the safety and tolerability of S65487 when combined with azacitidine
  2. To find the right dose for future studies
  3. To assess how effective the combination is in treating AML

The trial will measure various outcomes, including:

  • Complete Remission (CR) rate: This measures how many patients have no detectable leukemia cells after treatment.
  • Duration of Response (DOR): How long the positive effects of the treatment last.
  • Overall Survival (OS): How long patients live after starting the treatment.
  • Minimal Residual Disease (MRD): This looks for very small numbers of leukemia cells that may remain after treatment.[1]

Potential Benefits of S65487

While it’s important to note that S65487 is still in the testing phase, it holds promise for several reasons:

  • It may offer a new treatment option for AML patients who can’t receive intensive chemotherapy.
  • By targeting Bcl-2, it uses a different approach to fighting leukemia cells compared to traditional chemotherapy.
  • The combination with azacitidine may potentially enhance the effectiveness of treatment.

However, as with any experimental treatment, the full benefits and risks of S65487 will only be known after the completion of clinical trials.[1]

Aspect Details
Study Type Phase I/II, open-label, multi-center clinical trial
Target Condition Previously untreated acute myeloid leukemia (AML) in adults not eligible for intensive treatment
Treatment S65487 (Bcl2 inhibitor) combined with azacitidine
Primary Objectives Phase I: Determine safety, tolerability, and optimal dose
Phase II: Assess efficacy (Complete Remission rate)
Key Eligibility Criteria Adults ≥18 years, confirmed untreated AML, not eligible for standard induction chemotherapy
Main Outcome Measures Safety profile, Complete Remission rate, Duration of Response, Event-Free Survival, Progression-Free Survival, Overall Survival

FAQ

  • What is the main purpose of this clinical trial? The main purpose of this clinical trial is to evaluate the safety, effectiveness, and optimal dosage of S65487 (a Bcl2 inhibitor) combined with azacitidine in treating adult patients with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive treatment.
  • Who is eligible to participate in this trial? Eligible participants are adults aged 18 or older with confirmed, untreated AML who are not suitable for standard induction chemotherapy. This includes patients aged 75 or older, or those with specific health conditions that make intensive treatment risky.
  • What are the two phases of the trial? The trial has two phases: Phase I focuses on determining the safety profile, tolerability, and optimal dosage of S65487 combined with azacitidine. Phase II aims to assess the efficacy of this combination therapy in treating AML.
  • What is S65487 and how is it administered? S65487 is a Bcl2 inhibitor, which is a type of targeted therapy for cancer treatment. In this trial, it is administered as a solution for intravenous infusion, combined with azacitidine.
  • What are the main outcomes being measured in this trial? The main outcomes include safety assessments, determination of the optimal dose, and efficacy measures such as complete remission (CR) rate, duration of response, event-free survival, progression-free survival, and overall survival. The trial will also assess the depth and duration of response to the treatment.

Ongoing Clinical Trials on 4-{[(3S)-2-(4-Chloro-2-{4-[(5-Cyano-1,2-Dimethyl-1H-Pyrrol-3-Yl)(4-Hydroxyphenyl)Carbamoyl]-1,5-Dimethyl-1H-Pyrrol-2-Yl}Benzoyl)-1,2,3,4-Tetrahydroisoquinolin-3-Yl]Methyl}Morpholin-4-Ium Hydrogen Sulfate

  • Study on S65487 and Azacitidine for Adults with Untreated Acute Myeloid Leukemia Not Suitable for Intensive Treatment

    Not recruiting

    2 1 1 1
    Investigated drugs:
    France Spain

Glossary

  • Acute Myeloid Leukemia (AML): A type of cancer that affects the blood and bone marrow, characterized by the rapid growth of abnormal white blood cells that interfere with the production of normal blood cells.
  • Bcl2 inhibitor: A type of targeted therapy that blocks the action of Bcl2, a protein that helps cancer cells survive. By inhibiting Bcl2, these drugs can cause cancer cells to die.
  • Azacitidine: A chemotherapy drug used to treat certain blood cancers, including some types of myelodysplastic syndromes and acute myeloid leukemia.
  • Complete Remission (CR): A treatment response where all signs of cancer have disappeared, although cancer may still be present in the body at levels too low to detect.
  • Dose Limiting Toxicity (DLT): Side effects of a drug that are severe enough to prevent an increase in dosage or require a decrease in dosage.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug that can be given without causing unacceptable side effects.
  • Recommended Phase II Dose (RP2D): The dose of a drug determined in Phase I trials to be appropriate for further testing in Phase II trials.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • ECOG Performance Status: A scale used to assess how a patient's disease is progressing and how it affects daily living abilities.
  • Minimal Residual Disease (MRD): The small number of cancer cells that may remain in the body during or after treatment, often undetectable by standard tests.

References

  1. http://clinicaltrials.eu/trial/study-on-s65487-and-azacitidine-for-adults-with-untreated-acute-myeloid-leukemia-not-suitable-for-intensive-treatment/