What is the mechanism of action of this treatment?

The most common treatments for Primary Myelofibrosis (PMF) include JAK inhibitors such as ruxolitinib and experimental therapies like selinexor. Ruxolitinib works by inhibiting the JAK-STAT pathway, which is often overactive in PMF, thereby reducing inflammation and splenomegaly, and improving symptoms and quality of life. Selinexor, a Selective Inhibitor of Nuclear Export, blocks the export of tumor suppressor proteins from the nucleus, leading to the accumulation of these proteins in the nucleus and inducing cancer cell death. These treatments are crucial for PMF patients as they target the underlying disease mechanisms, potentially slowing disease progression and alleviating symptoms.

What side effects are associated with this type of intervention?

Common treatments for Primary Myelofibrosis include JAK1/2 inhibitors like ruxolitinib, which can cause side effects such as anemia, thrombocytopenia, and increased risk of infections. Another treatment option is hydroxyurea, which may lead to cytopenias and gastrointestinal disturbances. For patients intolerant or refractory to JAK inhibitors, Selinexor, a Selective Inhibitor of Nuclear Export, is being studied. Known side effects of Selinexor include nausea, fatigue, anorexia, and thrombocytopenia. These treatments aim to manage symptoms and improve quality of life but come with significant side effect profiles that need to be managed carefully.

What prior FDA approvals exist?

The FDA has approved several treatments for Primary Myelofibrosis (PMF). Ruxolitinib, a JAK1/2 inhibitor, is one of the primary treatments for PMF, targeting the JAK-STAT pathway to reduce symptoms and spleen size. Fedratinib, another JAK2 inhibitor, is also approved for patients with PMF, especially those who are resistant or intolerant to Ruxolitinib. While Selinexor, a Selective Inhibitor of Nuclear Export, is being studied for its efficacy in PMF, it is not yet FDA-approved for this indication. These treatments aim to manage symptoms and improve quality of life for patients with PMF.

What other types of research exist?

Promising novel alternatives to Selinexor for Primary Myelofibrosis patients include: 1) Ruxolitinib, a JAK1/2 inhibitor, which has shown efficacy in reducing spleen size and alleviating symptoms in PMF patients. 2) Fedratinib, another JAK2 inhibitor, which is effective for patients who are resistant or intolerant to Ruxolitinib. 3) Luspatercept, an erythroid maturation agent, which is being explored for its potential to improve anemia in MPNs. 4) Venetoclax, a BCL2 inhibitor, which is being studied in combination with other agents for its potential in treating myeloid malignancies. These alternatives offer different mechanisms of action and have shown promise in clinical settings.

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Selective Inhibitor of Nuclear Export (SINE)

Selinexor for Myelofibrosis (ESSENTIAL Trial)

Phase 2

Waitlist Available

Led By Srinivas Tantravahi, MD

Research Sponsored by University of Utah

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

Diagnosis of primary myelofibrosis (PMF), post-essential thrombocytosis (PET-MF) or post-polycythemia vera (PPV-MF)

Must not have

Major surgery ≤ 4 weeks prior to C1D1

BSA < 1.4 m2 at baseline, calculated by the Dubois or Mosteller methods

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5.5 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing selinexor, a medication that may help treat certain blood disorders. It focuses on patients with primary or secondary myelofibrosis who do not respond to or cannot tolerate common treatments like ruxolitinib. Selinexor works by blocking a protein that helps harmful cells grow and survive. Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment.

Who is the study for?

Adults diagnosed with primary or secondary myelofibrosis who haven't responded well to, or can't tolerate, JAK1/2 inhibitors like ruxolitinib. They should be relatively active (ECOG ≤ 2), have a spleen enlarged by at least 5 cm if symptomatic or 10 cm regardless of symptoms, and meet specific blood count and organ function criteria.

What is being tested?

The trial is testing Selinexor's effectiveness and safety in patients with myelofibrosis who don't benefit from current treatments. It's an open-label study where all participants receive the drug; there's no comparison group.

What are the potential side effects?

Selinexor may cause nausea, vomiting, diarrhea, loss of appetite, weight loss, fatigue, low blood counts leading to increased risk of infections or bleeding problems. Some people might also experience changes in liver enzymes indicating liver stress.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself and am up and about more than 50% of my waking hours.

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I have been diagnosed with a type of myelofibrosis.

Exclusion Criteria

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

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I have not had major surgery in the last 4 weeks.

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My body surface area is less than 1.4 square meters.

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I have no stomach or bowel problems affecting my ability to swallow pills.

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I am breastfeeding and cannot stop during the study.

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I do not have an active hepatitis A, B, or C infection.

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I haven't had cancer treatment in the last 2 weeks.

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I am allergic or cannot take certain medications needed for the trial.

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I have previously been treated with a SINE compound like selinexor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5.5 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5.5 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5.5 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

Count of Participants With Reduction in Spleen Volume

Secondary study objectives

Adverse Events That Occur

Change in Symptoms Score

Overall Response

+2 more

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562

50%

Thrombocytopenia

45%

Anaemia

39%

Nausea

29%

Decreased appetite

29%

Diarrhoea

27%

Weight decreased

24%

Neuropathy peripheral

24%

Vomiting

23%

Fatigue

21%

Neutropenia

21%

Cataract

15%

Asthenia

12%

Upper respiratory tract infection

11%

Pyrexia

11%

Constipation

Oedema peripheral

Pneumonia

Lymphopenia

Dizziness

Insomnia

Dehydration

Back pain

Leukopenia

Bronchitis

Cough

Acute kidney injury

Abdominal pain

Muscular weakness

Lower respiratory tract infection

Pain in extremity

Sepsis

Hyperglycaemia

Urinary tract infection

Nasopharyngitis

Hyponatraemia

Toothache

Disturbance in attention

Cardiac failure

Hypertension

Peripheral swelling

Haemoglobin decreased

Blood uric acid increased

Cardiac failure acute

Pulmonary contusion

Embolism

Blood creatinine increased

Paraesthesia

Infection

Respiratory syncytial virus infection

Dyspepsia

Syncope

Clostridium difficile infection

Compression fracture

Multiple fractures

Myocardial infarction

C-reactive protein increased

Cerebral haemorrhage

Ischaemic stroke

Sudden death

Oropharyngeal pain

Cognitive disorder

Confusional state

Influenza

Septic shock

Osteonecrosis of jaw

Taste disorder

Hyperkalaemia

Depression

Cerebrovascular accident

Bronchitis viral

100%

80%

60%

40%

20%

Study treatment Arm

SVdX Arm: Selinexor + Bortezomib + Dexamethasone

SdX Arm: Selinexor + Dexamethasone

SVd Arm: Selinexor + Bortezomib + Dexamethasone

Vd Arm: Bortezomib + Dexamethasone

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: Selinexor, all patientsExperimental Treatment1 Intervention

Single Arm Study, all patients will get selinexor

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selinexor

2020

Completed Phase 3

~1730

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

The most common treatments for Primary Myelofibrosis (PMF) include JAK inhibitors such as ruxolitinib and experimental therapies like selinexor. Ruxolitinib works by inhibiting the JAK-STAT pathway, which is often overactive in PMF, thereby reducing inflammation and splenomegaly, and improving symptoms and quality of life. Selinexor, a Selective Inhibitor of Nuclear Export, blocks the export of tumor suppressor proteins from the nucleus, leading to the accumulation of these proteins in the nucleus and inducing cancer cell death. These treatments are crucial for PMF patients as they target the underlying disease mechanisms, potentially slowing disease progression and alleviating symptoms.

[Myelofibrosis: A review].Rescue of a primary myelofibrosis model by retinoid-antagonist therapy.