What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia, such as hypomethylating agents like azacitidine, are associated with several side effects. These include cytopenias (low blood cell counts), febrile neutropenia (fever with low white blood cell count), thrombocytopenia (low platelet count), anemia, and infections. Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation are also frequent. Novel drug combinations, like those involving S64315, may have similar side effects, with additional risks depending on the specific drug's mechanism of action and patient response.

What prior FDA approvals exist?

Azacitidine, a hypomethylating agent, is FDA-approved for treating AML, especially in patients unsuitable for intensive chemotherapy. Oral azacitidine (CC-486) is also approved for maintenance therapy in AML patients in first remission. While decitabine is approved by the EMA, it is not FDA-approved for AML. Venetoclax, often combined with azacitidine or decitabine, has shown efficacy in AML treatment. These approvals underscore the importance of hypomethylating agents and their combinations in managing AML.

What other types of research exist?

Promising novel alternatives for AML treatment include combinations of hypomethylating agents (HMAs) with venetoclax or ivosidenib. These combinations have shown improved outcomes compared to HMA monotherapy. Specifically, HMA plus venetoclax and HMA plus ivosidenib have demonstrated clinical benefits in terms of overall survival and response rates.

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Anti-metabolites

S64315 + Azacitidine for Acute Myeloid Leukemia

Phase 1 & 2

Waitlist Available

Research Sponsored by Institut de Recherches Internationales Servier

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 ≤ 2.

Patients aged ≥ 18 years

Must not have

Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.

Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up an average of 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment that combines two drugs, S64315 and azacitidine, to see if they are safe and effective for patients with acute myeloid leukemia. S64315 may help kill cancer cells, while azacitidine helps stop them from growing. The goal is to find better treatment options for this type of blood and bone marrow cancer.

Who is the study for?

This trial is for adults with acute myeloid leukemia (AML) who haven't been treated before and can't have intensive chemo, or those whose AML has returned or didn’t respond to treatment. Participants need to be in fairly good health otherwise, with a performance status of ≤2 on the ECOG scale and proper organ function.

What is being tested?

The trial is testing the combination of S64315 (MIK665) and azacitidine to see if they're safe together, how well patients tolerate them, and their effectiveness against AML. It's an early-phase study which means it’s partly about finding the right dose as well as checking for benefits.

What are the potential side effects?

While specific side effects aren’t listed here, common ones from drugs like S64315 and azacitidine may include nausea, vomiting, fatigue, fever, low blood counts leading to increased infection risk or bleeding problems. Organ-specific inflammation could also occur.

Eligibility Criteria

Inclusion Criteria

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

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I am able to care for myself and perform daily activities.

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I am 18 years old or older.

Exclusion Criteria

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

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I do not have HIV, significant liver disease, active pancreatitis, or CNS disease.

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My blood pressure is not higher than 150/95 mmHg.

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I do not have any severe or uncontrolled infections.

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I have had a myeloproliferative syndrome in the past.

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I do not have uncontrolled hepatitis B or C.

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I have recovered from side effects of previous cancer treatments, except for hair loss.

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I have been treated with an Mcl-1 inhibitor before.

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I do not have serious heart problems like heart failure or an LVEF below 50%.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ an average of 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~an average of 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and an average of 6 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

Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)

Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)

Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)

Secondary study objectives

Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)

Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)

Side effects data

From 2023 Phase 1 & 2 trial • 17 Patients • NCT04629443

80%

Febrile neutropenia

80%

Alanine aminotransferase increased

80%

Constipation

40%

Aspartate aminotransferase increased

40%

Hypokalaemia

40%

Hypophosphataemia

40%

Oedema peripheral

40%

Anaemia

40%

Neutropenia

40%

Thrombocytopenia

20%

Folliculitis

20%

Herpes simplex reactivation

20%

Pneumonia

20%

Sepsis

20%

Anorectal cellulitis

20%

Bacteraemia

20%

Device related infection

20%

Escherichia bacteraemia

20%

Leukocytosis

20%

Upper gastrointestinal haemorrhage

20%

Troponin T increased

20%

Blood bilirubin increased

20%

Blood creatinine increased

20%

Diarrhoea

20%

Abdominal pain

20%

Haemorrhoids

20%

Nausea

20%

Abdominal pain upper

20%

Aphthous ulcer

20%

Gingival bleeding

20%

Haemorrhoidal haemorrhage

20%

Vomiting

20%

Hypomagnesaemia

20%

Pyrexia

20%

Administration site erythema

20%

Injection site rash

20%

Dysuria

20%

Urinary incontinence

20%

Headache

20%

Epistaxis

20%

Spinal osteoarthritis

100%

80%

60%

40%

20%

Study treatment Arm

50 mg S64315 (Also Referred as MIK665) With Azacitidine

100 mg S64315 (Also Referred as MIK665) With Azacitidine

190 mg S64315 (Also Referred as MIK665) With Azacitidine

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: S64315 (also referred as MIK665) with azacitidineExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

S 64315 (also referred as MIK665) and azacitidine

2021

Completed Phase 2

~20

0 / 10Eligibility 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

Hypomethylating agents like azacitidine inhibit DNA methyltransferase, leading to DNA hypomethylation and reactivation of tumor suppressor genes, which can induce differentiation and apoptosis in leukemic cells. Novel drugs such as S64315 often target specific proteins involved in cell survival pathways, promoting apoptosis in cancer cells. These mechanisms are crucial for AML patients as they help in selecting targeted therapies that effectively disrupt the growth and survival of leukemic cells, potentially improving treatment outcomes.

Role of epigenetic in leukemia: From mechanism to therapy.Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia.Molecular targeting in acute myeloid leukemia.