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

Q: What is the mechanism of action of this treatment?

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.

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.

Must not have

Subject has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke or left ventricular ejection fraction (LVEF) <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.

Female subject who is pregnant or lactating.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing E7820, a new type of oral medication for treating blood cancers in patients whose cancers have come back or did not respond to previous treatments and have certain genetic changes. The drug works by targeting faulty genetic processes in cancer cells to stop their growth.

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.

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.

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.

Select...

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

Select...

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

Select...

My MDS has returned after initially responding to treatment.

Select...

My AML has returned after initial treatment success.

Select...

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

Select...

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

Select...

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

Exclusion Criteria

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

Select...

I haven't had serious heart issues like heart failure, heart attack, or stroke in the last 6 months.

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I am currently pregnant or breastfeeding.

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I have a condition that affects my ability to swallow or absorb pills.

Select...

I have been diagnosed with acute promyelocytic leukemia.

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I have an ongoing infection that hasn't improved with treatment.

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I have severe, life-threatening complications from my blood cancer.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

response rate

Side effects data

From 2017 Phase 1 trial • 45 Patients • NCT01773421

33%

Fatigue

33%

Blood bilirubin increased

27%

Decreased appetite

27%

Constipation

27%

Alanine aminotransferase increased

20%

Cough

20%

Dyspepsia

20%

Dry skin

20%

Pruritus

13%

Vomiting

13%

Oedema peripheral

13%

Pyrexia

13%

Upper respiratory tract infection

13%

Blood alkaline phosphatase increased

13%

Abdominal pain

13%

Stomatitis

13%

Nasopharyngitis

13%

Hyponatraemia

13%

Muscle spasms

13%

Lethargy

13%

Nausea

13%

Diarrhoea

13%

Aspartate aminotransferase increased

13%

Hyperglycaemia

Abdominal mass

Leukopenia

Thirst

Neutrophil count increased

Platelet count decreased

Joint swelling

Depressed mood

Bronchitis

Headache

Abdominal pain upper

Neutropenia

Conjunctivitis

Thrombocytopenia

Malaise

Food allergy

Haemorrhoids

Mouth ulceration

Oral candidiasis

Rhinitis

Blood creatinine increased

Blood magnesium decreased

Blood potassium decreased

Lipase increased

Weight decreased

White blood cell count increased

Musculoskeletal pain

Trismus

Dry throat

Dyspnoea

Epistaxis

Palmar-plantar erythrodysaesthesia syndrome

Urinary tract infection

Myopia

Myalgia

Oropharyngeal pain

Painful respiration

Nail disorder

Ocular hyperaemia

Anaemia

Blood glucose increased

Back pain

Nocturia

Rhinorrhoea

Alopecia

Tongue ulceration

Dehydration

100%

80%

60%

40%

20%

Study treatment Arm

Extension Phase Part A: E7820 100 mg

Treatment and Extension Phase Part B: E7820 50 mg

Treatment and Extension Phase Part B: E7820 60 mg

Treatment Phase Part A: E7820 50 mg Fed

Treatment Phase Part A: E7820 50 mg Fasted

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: 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 / 16Eligibility 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.