What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include cytotoxic chemotherapy, targeted therapies, and novel agents such as angiogenesis inhibitors. These treatments often come with significant side effects. Cytotoxic chemotherapy can cause severe hematologic toxicities like neutropenia, anemia, and thrombocytopenia, leading to increased infection risk and bleeding. Targeted therapies, including tyrosine kinase inhibitors and hypomethylating agents, may cause gastrointestinal issues, fatigue, and skin reactions. Novel agents like angiogenesis inhibitors, similar to E7820, can also lead to hypertension, proteinuria, and thromboembolic events. Balancing efficacy and managing these side effects is crucial in AML treatment.

What prior FDA approvals exist?

FDA-approved treatments for Acute Myeloid Leukemia (AML) include several targeted therapies and combination regimens. Venetoclax, an orally available BCL2 inhibitor, is approved in combination with hypomethylating agents (HMAs) like azacitidine or decitabine for newly diagnosed AML in patients ineligible for intensive chemotherapy. Ivosidenib, an IDH1 inhibitor, is another approved agent used in combination with HMAs. While E7820, an angiogenesis inhibitor targeting integrin α2, is still under investigation, other angiogenesis inhibitors like regorafenib have shown acceptable safety profiles and modest efficacy in relapsed/refractory myeloid malignancies. These treatments represent a growing arsenal of targeted therapies aimed at improving outcomes in AML.

What other types of research exist?

Promising novel alternatives to E7820 for AML patients include: 1) Venetoclax in combination with hypomethylating agents (HMAs) like azacitidine or decitabine, which has shown improved outcomes in clinical trials. 2) Ivosidenib for patients with IDH1 mutations, which has demonstrated efficacy in clinical settings. 3) KPT-276, a CRM1 inhibitor, which has shown significant preclinical activity in AML models. 4) Azacitidine plus gilteritinib, particularly for patients with FLT3 mutations, which has shown higher overall response rates in clinical trials.

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Splicing Modulator

E7820 for Leukemia

Phase 2

Waitlist Available

Led By Eytan Stein, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Refractory CMML is defined as: Failure to achieve a response (as per IWG 2006 criteria) after 4 cycles of HMA monotherapy or 2 cycles of HMA + venetoclax.

Relapsed CMML is defined as: Any relapse after achieving an IWG defined response.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

Study Summary

This trial is testing whether E7820 is an effective treatment for myeloid cancers that have relapsed or are resistant to other treatments.

Who is the study for?

Adults with relapsed or refractory myeloid cancers, specifically AML, MDS, or CMML that have certain splicing factor gene mutations. They must have tried specific treatments without success and should not be pregnant or breastfeeding. Participants need to be in a stable enough condition to follow the study schedule.Check my eligibility

What is being tested?

The trial is testing E7820's effectiveness for those with myeloid cancers who've had previous treatment failures. It focuses on patients whose cancer has returned after remission or hasn't responded to standard therapies.See study design

What are the potential side effects?

While the specific side effects of E7820 are not listed here, similar medications often cause fatigue, nausea, increased risk of infection due to low blood cell counts, bleeding complications, and potential liver issues.

Eligibility Criteria

Inclusion Criteria

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

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My CMML did not improve after specific treatments.

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My CMML cancer has returned after initially responding to treatment.

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I am 18 years old or older.

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My blood cancer has returned or didn't respond to treatment, and I have a specific genetic mutation.

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My kidney function is good and my liver is not severely damaged.

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My MDS has returned after initially responding to treatment.

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My AML has returned after initial treatment success.

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I have tried and cannot tolerate approved treatments for my FLT3, IDH1, or IDH2 mutation.

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I can care for myself but may not be able to do heavy physical work.

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My AML did not respond to at least two treatment cycles.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

response rate

Side effects data

From 2017 Phase 1 trial • 45 Patients • NCT01773421

53%

Fatigue

53%

Diarrhoea

42%

Anaemia

37%

Decreased appetite

37%

Lethargy

37%

Constipation

32%

Insomnia

32%

Abdominal pain

32%

Dizziness

26%

Vomiting

26%

Nausea

26%

Weight decreased

21%

Pyrexia

21%

Back pain

16%

Blood alkaline phosphatase increased

16%

Oedema peripheral

16%

Hyperglycaemia

16%

Headache

16%

Cough

16%

Rash

16%

Musculoskeletal chest pain

16%

Alanine aminotransferase increased

16%

Dry skin

11%

Upper respiratory tract infection

11%

Gastroenteritis

11%

Tachycardia

11%

Dyspnoea

11%

Nasopharyngitis

11%

Urinary tract infection

11%

Aspartate aminotransferase increased

11%

Blood albumin decreased

11%

Hypokalaemia

11%

Hypomagnesaemia

11%

Hyponatraemia

11%

Muscle spasms

11%

Myalgia

11%

Epistaxis

11%

Decubitus ulcer

11%

Hypertension

11%

Abdominal discomfort

11%

Dyspepsia

11%

Lower respiratory tract infection

11%

Ascites

Paraesthesia

Skin lesion

Inappropriate antidiuretic hormone secretion

Necrosis

Thirst

Pain in extremity

Haematuria

Tinnitus

Myopathy

Blood thyroid stimulating hormone increased

Phlebitis

Pancreatic enzyme abnormality

Osteomyelitis

Rash pustular

Bladder spasm

Erysipelas

Urosepsis

Hepatic enzyme abnormal

Tumour haemorrhage

Pruritus

Orthostatic hypotension

Muscle abscess

Atrioventricular block

Hyperthyroidism

Conjunctivitis

Clostridium difficile infection

Gastrooesophageal reflux disease

Pancreatitis

Upper gastrointestinal haemorrhage

Chest discomfort

Facial pain

Influenza like illness

Local swelling

Malaise

Nail infection

Oral herpes

Skin infection

Contusion

Wound haemorrhage

Blood glucose increased

Blood lactate dehydrogenase increased

Blood potassium decreased

Gamma-glutamyltransferase increased

Lipase increased

Protein total decreased

Vitamin D decreased

Dehydration

Type 2 diabetes mellitus

Arthralgia

Arthritis

Bone pain

Bursitis

Musculoskeletal pain

Dizziness postural

Affect lability

Dysphonia

Dyspnoea exertional

Wheezing

Erythema

Night sweats

Onychomadesis

Skin fissures

Haemoptysis

Blood phosphorus decreased

Thrombocytopenia

Feeling cold

Blood bilirubin increased

Cognitive disorder

Neuralgia

Scab

Dysphagia

Hypothyroidism

Abdominal distension

Duodenal ulcer haemorrhage

Pulmonary embolism

Asthenia

Otitis media

Fall

Procedural hypotension

Blood cholesterol increased

Hypocalcaemia

Anxiety

Nipple pain

Haemorrhage

Hypotension

100%

80%

60%

40%

20%

Study treatment Arm

Treatment and Extension Phase Part B: E7820 50 mg

Treatment and Extension Phase Part B: E7820 60 mg

Extension Phase Part A: E7820 100 mg

Treatment Phase Part A: E7820 50 mg Fed

Treatment Phase Part A: E7820 50 mg Fasted

Trial Design

1Treatment groups

Experimental Treatment

Group I: E7820Experimental Treatment1 Intervention

Each patient will receive daily administration of E7820. The starting dose for every patient will be 100 mg daily but the dose can subsequently be reduced if excessive toxicity is encountered.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

E7820

2011

Completed Phase 1

~50

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

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents (HMAs) such as azacitidine and decitabine, which work by inhibiting DNA methylation, thereby reactivating tumor suppressor genes and inducing cancer cell death. Angiogenesis inhibitors, like E7820, target integrin α2 to disrupt the blood supply to the tumor, inhibiting its growth and survival. These mechanisms are crucial for AML patients as they offer targeted approaches to halt disease progression, improve survival rates, and potentially reduce side effects compared to traditional chemotherapy.

Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia.Progress in the problem of relapsed or refractory acute myeloid leukemia.Molecular targeting in acute myeloid leukemia.