What side effects are associated with this type of intervention?

Common treatments for Myelofibrosis, such as JAK inhibitors like ruxolitinib and fedratinib, have several known side effects. Ruxolitinib can cause anemia, thrombocytopenia, and an increased risk of infections, including herpes zoster. Fedratinib has been associated with gastrointestinal symptoms, such as nausea and diarrhea, as well as serious hematologic toxicities like anemia and thrombocytopenia. Both treatments may also lead to liver impairment and elevated liver enzymes. These side effects highlight the importance of careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelofibrosis, primarily focusing on Janus kinase (JAK) inhibitors. Ruxolitinib, a JAK1/2 inhibitor, was one of the first approved and remains a cornerstone of Myelofibrosis treatment. Fedratinib, another JAK2 inhibitor, has also been approved for patients with intermediate-2 or high-risk Myelofibrosis. These treatments help manage symptoms and reduce spleen size. Selinexor, a Selective Inhibitor of Nuclear Export (SINE), is currently being studied for its efficacy and safety in Myelofibrosis patients who have been previously treated with JAK inhibitors, offering a potential new therapeutic option.

What other types of research exist?

Promising novel alternatives to Selinexor for Myelofibrosis patients include JAK inhibitors such as Ruxolitinib and Fedratinib, which have shown efficacy in clinical trials. Additionally, investigational agents like Navitoclax (a BCL-2 inhibitor) and Pelabresib (a BET inhibitor) are being studied for their potential benefits in treating Myelofibrosis.

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Selective Inhibitor of Nuclear Export (SINE)

Selinexor for Myelofibrosis

Phase 2

Waitlist Available

Research Sponsored by Karyopharm Therapeutics Inc

Eligibility Criteria Checklist

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

Must have

Measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥450 centimeter cube (cm^3) by magnetic resonance imaging (MRI) or computerized tomography (CT) scan

Calculated creatinine clearance (CrCl) >15 milliliter (mL)/minute (min) based on the Cockcroft and Gault formula.

Must not have

Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) grade >1)

Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to selinexor dosing or strong CYP3A inducers ≤14 days prior to selinexor dosing

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing selinexor, a medication that aims to stop harmful cells from growing, in patients with myelofibrosis. Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment, showing broad antitumor activity. These patients have already tried another treatment for a significant period without full success. The study will compare selinexor to other treatments chosen by doctors to see which works better.

Who is the study for?

Adults diagnosed with myelofibrosis who have been treated with JAK inhibitors for at least 6 months can join. They must be in good general health, not pregnant or breastfeeding, and willing to use contraception. People cannot join if they have a high percentage of blasts in blood or bone marrow, severe gastrointestinal issues affecting drug absorption, recent major surgery, life-threatening conditions, or previous treatment with selinexor.

What is being tested?

The trial is testing the safety and effectiveness of Selinexor compared to other treatments chosen by physicians for those with myelofibrosis previously treated with JAK inhibitors. Participants will be randomly assigned to either receive Selinexor or a physician's choice treatment in an open-label study.

What are the potential side effects?

Selinexor may cause side effects such as nausea, vomiting, diarrhea (if severe), fatigue, blood count changes that could lead to increased risk of infections or bleeding problems. The exact side effects depend on individual reactions and the specific treatments used in the physician's choice group.

Eligibility Criteria

Inclusion Criteria

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

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My spleen is enlarged, measuring over 450 cm^3 on an MRI or CT scan.

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My kidneys are functioning well enough for treatment.

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I am able to get out of my bed or chair and move around.

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I have been diagnosed with a specific type of blood cancer (MF, post-ET MF, or post-PV MF) as per WHO guidelines.

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I am 18 years old or older.

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I have been treated with JAK inhibitors for at least 6 months.

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I am 18 years old or older.

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I have been diagnosed with a specific type of blood cancer according to the latest WHO guidelines.

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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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My spleen is enlarged, measuring over 450 cm^3 on an MRI or CT scan.

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I have been treated with JAK inhibitors for at least 6 months.

Exclusion Criteria

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

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I do not have severe GI issues that could affect medication absorption.

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I haven't taken strong CYP3A affecting drugs within the last week.

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My blood or bone marrow has a high number of immature cells.

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I am not pregnant or breastfeeding.

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I am not allergic or unable to take selinexor or the drugs in the study.

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I have been treated with selinexor or similar drugs before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562

43%

Weight decreased

29%

Cough

29%

Thrombocytopenia

29%

Nausea

29%

Decreased appetite

21%

Anaemia

21%

Fatigue

21%

Constipation

21%

Diarrhoea

14%

Oedema peripheral

14%

Pneumonia

14%

Neuropathy peripheral

14%

Paraesthesia

14%

Cataract

14%

Vomiting

14%

Headache

Fungal skin infection

Urinary tract infection

Asthma

Disturbance in attention

Respiratory syncytial virus infection

Neutropenia

Peripheral swelling

Mental status changes

Lower respiratory tract infection

Hyperthyroidism

Back pain

Pain in extremity

Hyponatraemia

Skin lesion

Oropharyngeal pain

Pyrexia

Cardiac failure

Hepatitis

Pharyngitis

Pollakiuria

Non-cardiac chest pain

C-reactive protein increased

Taste disorder

Haemorrhagic transformation stroke

Abdominal pain

Insomnia

Dyspepsia

Haemoglobin decreased

Infection

Hyperglycaemia

Toothache

Ecchymosis

Upper respiratory tract infection

Nasopharyngitis

Viral infection

Hypertension

Muscular weakness

Bronchiectasis

Basal cell carcinoma

Hypophagia

100%

80%

60%

40%

20%

Study treatment Arm

SdX Arm: Selinexor + Dexamethasone

SVdX Arm: Selinexor + Bortezomib + 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

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm S: SelinexorExperimental Treatment1 Intervention

Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive a dose of selinexor 80 mg for first 2 cycles followed by selinexor 60 mg once weekly (QW) in subsequent cycles orally on Days 1, 8, 15, and 22 of each 28-day cycle to participants on Arm S.

Group II: Arm PC: Physician's Choice TreatmentActive Control1 Intervention

Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive Physician's choice treatment which will be administered as per clinical practice.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selinexor

2020

Completed Phase 3

~1730

0 / 17Eligibility 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 Myelofibrosis include JAK inhibitors such as ruxolitinib and fedratinib, and selective inhibitors of nuclear export like selinexor. JAK inhibitors work by blocking the Janus kinase (JAK) pathway, which is often overactive in Myelofibrosis, leading to reduced inflammation and spleen size, and improved symptoms. Selinexor, on the other hand, inhibits the export of tumor suppressor proteins from the nucleus, thereby promoting cancer cell death. These mechanisms are crucial for Myelofibrosis patients as they target the underlying disease processes, potentially improving survival and quality of life.

Targeting myeloproliferative neoplasms with JAK inhibitors.