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Janus Kinase (JAK) Inhibitor

Selinexor + Ruxolitinib for Myelofibrosis (SENTRY Trial)

Phase 3

Recruiting

Research Sponsored by Karyopharm Therapeutics Inc

Eligibility Criteria Checklist

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

Must have

Participants with international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk.

A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (PV) MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.

Must not have

History of pulmonary hypertension.

Participants unable to tolerate two forms of antiemetics prior to each dose for at least 2 cycles.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new combination drug therapy for myelofibrosis, a bone marrow cancer. The trial will have three phases, with the first two phases testing safety and preliminary efficacy in various doses, and the third phase testing efficacy in a randomized study.

Who is the study for?

Adults diagnosed with primary or secondary myelofibrosis, showing significant spleen enlargement and certain risk levels. They must have functioning major organs, no prior treatments with JAK inhibitors or selinexor, not be pregnant or breastfeeding, agree to use contraception, and have a life expectancy over 6 months. Exclusions include recent surgeries, uncontrolled infections without stable treatment for hepatitis B/C or HIV.

What is being tested?

The trial is testing the combination of Selinexor and Ruxolitinib against a placebo plus Ruxolitinib in patients who haven't used JAK inhibitors before. It's split into two phases: an initial phase to determine safe dosages followed by a larger phase where participants are randomly assigned to either the drug combo or placebo in a 2:1 ratio.

What are the potential side effects?

Potential side effects may include digestive issues like nausea and diarrhea; blood disorders such as low platelet counts; liver function abnormalities; fatigue; possible allergic reactions if sensitive to the drugs' components; and increased risk of infection due to immune system effects.

Eligibility Criteria

Inclusion Criteria

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

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My condition is classified as intermediate-1, intermediate-2, or high-risk according to DIPSS.

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I have been diagnosed with a specific type of bone marrow disorder according to the latest standards.

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My liver tests are within the normal range.

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I have HIV with a CD4+ count >= 350, no AIDS infections in the last year, and have been on ART for at least 4 weeks.

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I have significant symptoms of myelofibrosis according to the MFSAF V4.0.

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I am not eligible for a stem cell transplant.

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My spleen is enlarged, measuring over 450 cm^3 on a recent scan.

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I had hepatitis C but have been treated and now have an undetectable viral load.

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

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I am 18 years old or older.

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My white blood cell count is healthy without needing medication to boost it.

Exclusion Criteria

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

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I have a history of high blood pressure in the lungs.

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I cannot tolerate two different anti-nausea medications for at least 2 treatment cycles.

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I have been treated with selinexor or similar drugs before.

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I haven't had serious heart issues or strokes in the last 6 months.

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I am not allergic to selinexor, ruxolitinib, or their ingredients.

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

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I have been treated with JAK inhibitors for myelofibrosis.

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I am not pregnant or breastfeeding.

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

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%

Constipation

21%

Diarrhoea

21%

Fatigue

14%

Oedema peripheral

14%

Pneumonia

14%

Neuropathy peripheral

14%

Paraesthesia

14%

Cataract

14%

Vomiting

14%

Headache

Fungal skin infection

Asthma

Respiratory syncytial virus infection

Neutropenia

Lower respiratory tract infection

Urinary tract infection

Back pain

Peripheral swelling

Mental status changes

Hyperthyroidism

Pain in extremity

Hyponatraemia

Skin lesion

Oropharyngeal pain

Pyrexia

Disturbance in attention

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

Hypophagia

Basal cell carcinoma

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Phase 3: Selinexor 60 mg + Ruxolitinib BIDExperimental Treatment2 Interventions

Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group II: Phase 1b: Selinexor and Ruxolitinib BIDExperimental Treatment2 Interventions

Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group III: Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BIDExperimental Treatment2 Interventions

Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group IV: Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BIDExperimental Treatment2 Interventions

Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.

Group V: Phase 3: Placebo + Ruxolitinib BIDActive Control2 Interventions

Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selinexor

2020

Completed Phase 3

~1730

Ruxolitinib

2018

Completed Phase 3

~1170