Ruxolitinib for Thrombocythemia and Polycythemia

Recruiting at 3 trial locations

Overseen By Gabriela Hobbs, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Acyclovir

Must not be taking: Strong 3A4 inhibitors

Disqualifiers: High-risk ET/PV, Splenectomy, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug ruxolitinib can reduce symptoms in people with low-risk essential thrombocythemia (ET) and polycythemia vera (PV). These conditions cause the body to produce too many blood cells, leading to issues like fatigue and headaches. Participants take ruxolitinib twice daily over several cycles. People diagnosed with ET or PV who experience significant symptoms might be a good fit for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from an innovative therapy.

Will I have to stop taking my current medications?

If you are currently taking cytoreductive therapy (medications that reduce blood cell counts), you will need to stop them at least 7 days before starting the trial drug, ruxolitinib. Additionally, you cannot take medications that strongly inhibit a specific liver enzyme (3A4 isozyme), so you should discuss all your current medications with the study team.

Is there any evidence suggesting that ruxolitinib is likely to be safe for humans?

Research has shown that ruxolitinib is usually well-tolerated by patients with conditions like polycythemia vera (PV). One study compared ruxolitinib to other treatments and found that patients taking ruxolitinib experienced fewer non-blood-related side effects and fewer blood clots. Over time, the most common side effect was low levels of red blood cells, known as anemia. Overall, these findings suggest that ruxolitinib is safe for many patients, although it can cause low blood counts. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Ruxolitinib for thrombocythemia and polycythemia because it targets the JAK-STAT pathway, which is a new approach compared to traditional treatments like hydroxyurea and aspirin. Unlike these standard treatments that primarily aim to reduce blood cell production and clotting risk, Ruxolitinib specifically inhibits JAK2, a protein involved in the overproduction of blood cells. This targeted mechanism has the potential to more effectively manage symptoms and improve patient outcomes by directly addressing the underlying cause of the disorder.

What evidence suggests that ruxolitinib might be an effective treatment for thrombocythemia and polycythemia?

Studies have shown that ruxolitinib effectively treats conditions like polycythemia vera (PV) by controlling red blood cell levels. One study found that 60% of patients using ruxolitinib managed their red blood cell levels, compared to only 20% with standard treatments. Ruxolitinib also reduces the need for frequent blood draws and decreases spleen size. Additionally, it lowers the risk of blood clots in patients. Overall, ruxolitinib shows promise in reducing symptoms and complications related to PV and essential thrombocythemia (ET). Participants in this trial will receive ruxolitinib in two stages, each focusing on different cohorts of patients with significant symptom burdens. ^{2 4 5 6 7}

Who Is on the Research Team?

Gabriela Hobbs, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults diagnosed with low-risk essential thrombocythemia or polycythemia vera, without a history of high-risk factors like thrombosis or certain mutations. Participants must have specific blood count levels, organ function within normal ranges, and no severe cardiac issues. They should not be on conflicting medications, pregnant, breastfeeding, or at risk of pregnancy without contraception.

Inclusion Criteria

I have chronic hepatitis B but it's under control with medication.

I have HIV but am on treatment and my viral markers are negative.

My essential thrombocythemia is classified as very low, low, or intermediate risk.

Exclusion Criteria

Patients with >5% blasts on baseline marrow exam or in peripheral blood

Participants with psychiatric illness/social situations limiting compliance with study requirements

History of allergic reactions to compounds of similar composition to ruxolitinib

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ruxolitinib 2x daily for 6 study cycles, each cycle lasting 28 days

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue to receive Ruxolitinib as long as there are no unacceptable side effects or disease progression

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The trial is testing Ruxolitinib's effectiveness in reducing symptoms of essential thrombocythemia and polycythemia vera. It involves patients who meet specific criteria for these conditions and requires them to have a particular symptom score before starting the treatment.

How Is the Trial Designed?

Group I: Ruxolitinib Stage 2 Experimental Treatment 1 Intervention

Stage 2 will commence based on 3 or more participants in Stage 1 showing a predetermined positive response to Ruxolitinib. In stage 2, participants will be divided into two cohorts: * Very low, Low, and Intermediate-risk ET patients with significant symptom burden and Low-risk PV patients with significant symptom burden * Study cycles are 28 days long, participants in both cohorts will receive: * Ruxolitinib 2x daily for 6 study cycles.

Group II: Ruxolitinib Stage 1 Experimental Treatment 1 Intervention

In stage 1, participants will be divided into two cohorts: * Very low, Low, and Intermediate-risk ETpatients with significant symptom burden and Low-risk PV patients with significant symptom burden * Study cycles are 28 days long, participants in both cohorts will receive: * Ruxolitinib 2x daily for 6 study cycles.

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8900057/

Real-World Outcomes of Ruxolitinib Treatment for ... Ruxolitinib demonstrated efficacy in reducing phlebotomy requirements and palpable splenomegaly. This is the first real-world review of patients with ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1409002

Ruxolitinib versus Standard Therapy for the Treatment ... Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in ...

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35661

Ten years of experience with ruxolitinib since approval for ... Thrombotic events occurred in 2.7% versus 4.2% of patients in the ruxolitinib group (median follow-up, 26 months) versus patients continuing on ...

4. investor.incyte.com investor.incyte.com/news-releases/news-release-details/new-phase-3-data-show-jakafir-ruxolitinib-superior-best

New Phase 3 Data Show Jakafi® (ruxolitinib) is Superior to ... The data show that Jakafi was superior to best available therapy (BAT) in maintaining hematocrit control (62.2% vs. 18.7%, respectively)

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4553/504603/Ruxolitinib-Treatment-in-Polycythemia-Vera-Results

Ruxolitinib Treatment in Polycythemia Vera Results in ... Ruxolitinib treatment in polycythemia vera results in reduction in JAK2 allele burden in addition to improvement in hematocrit control and symptom burden.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8938906/

Long-term efficacy and safety of ruxolitinib versus best ... Non-haematological adverse events were generally lower with long-term ruxolitinib treatment than with best available therapy. Thromboembolic events were lower ...

7. hcp.jakafi.com hcp.jakafi.com/polycythemia-vera/

For Adults with Polycythemia Vera (PV) MAJIC-PV study results: WBC control and risk of thrombosis. Dr Claire Harrison discusses findings from the RESPONSE and MAJIC-PV studies, including data on the ...