Ruxolitinib for Myelofibrosis

No longer recruiting at 5 trial locations

Overseen By Gabriela Hobbs, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Ruxolitinib

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Prior transplant, Heart failure, 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: 56

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Ruxolitinib (also known as Jakafi, Jakavi, or Opzelura) to determine its effectiveness in treating myelofibrosis, a bone marrow disorder affecting blood cell production. Researchers are examining the drug's efficacy for individuals with symptoms such as an enlarged spleen or other myelofibrosis-related issues. Participants will take Ruxolitinib orally every day in continuous cycles. Suitable candidates for this trial have been diagnosed with myelofibrosis and plan to undergo a specific type of stem cell transplant. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop all myelofibrosis-directed therapy except for ruxolitinib. If you are already on ruxolitinib, you can continue taking it during the study.

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

Research has shown that Ruxolitinib is generally well-tolerated by patients. Studies have found that the most common side effects are anemia, a low red blood cell count, and thrombocytopenia, a low platelet count. These side effects appear consistently across different studies. Importantly, these conditions do not typically worsen over time with continued treatment. Overall, Ruxolitinib effectively manages symptoms and reduces spleen size in patients with myelofibrosis, offering significant benefits despite these side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myelofibrosis?

Ruxolitinib is unique because it targets a specific pathway involved in myelofibrosis, called the JAK-STAT pathway. Unlike the standard treatments for myelofibrosis, which often include hydroxyurea or interferon, Ruxolitinib works by directly inhibiting the activity of JAK1 and JAK2 enzymes. This targeted action helps reduce symptoms and improve quality of life for patients by addressing the root cause of the disease's progression. Researchers are excited about Ruxolitinib because it offers a more precise approach to managing myelofibrosis, potentially leading to better patient outcomes compared to existing therapies.

What evidence suggests that Ruxolitinib might be an effective treatment for Myelofibrosis?

Research has shown that Ruxolitinib, which participants in this trial will receive, effectively treats myelofibrosis. In studies, about 45.9% of patients taking Ruxolitinib experienced significant symptom improvement, compared to only 5.3% of those taking a placebo (a pill with no active medicine). It also helps shrink the spleen and can extend life expectancy. Real-world evidence supports these benefits, demonstrating improved symptoms and longer survival. Overall, Ruxolitinib is considered a promising option for people with myelofibrosis. ^{2 6 7 8 9}

Who Is on the Research Team?

Gabriela Hobbs, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with primary or secondary myelofibrosis, who are either already taking Ruxolitinib or will start it. They must have symptoms like an enlarged spleen and meet certain blood count criteria. Participants should be fit enough for a stem cell transplant from a matched donor and not have severe organ damage, uncontrolled infections, heart failure, other recent cancers (except some skin cancers), or be pregnant.

Inclusion Criteria

I am eligible for or already on ruxolitinib for my enlarged spleen or symptoms, and my spleen has not grown >5 cm since starting treatment.

You are expected to live for at least 3 more months.

I am not on any treatment for myelofibrosis except ruxolitinib.

Exclusion Criteria

You have an allergy or extreme sensitivity to any medication that belongs to the JAK inhibitor family.

Patients without normal organ function defined as follows: AST (SGOT), ALT (SGPT) and Alkaline Phosphatase ≥ 3 × institutional Upper Limit of Normal (ULN), Direct bilirubin >2.0 mg/dL, Adequate renal function as defined by calculated creatinine clearance≤60 mL/min (Cockcroft-Gault formula), Have a chronic or active infection that requires systemic antibiotics, antifungal or antiviral treatment, Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF < 40%, as measured by MUGA scan or echocardiogram), Pregnancy at the time of enrollment, Unable to give informed consent, Have an uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study, Not able to take oral medication

My blood or bone marrow had a rapid increase in immature cells before my cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Treatment

Participants receive Ruxolitinib therapy before hematopoietic stem cell transplantation (HCT) based on their eligibility

2-6 months

Continuous dosing every 28 days

Post-Transplant Treatment

Participants receive Ruxolitinib therapy after HCT to assess efficacy and tolerability, and to examine GVHD rates

Up to 2 years

Continuous dosing every 28 days

Follow-up

Participants are monitored for GVHD free and relapse free survival, overall survival, and other outcomes

1-2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests the drug Ruxolitinib in patients with myelofibrosis before, during, and after they receive a hematopoietic stem cell transplant (HSCT). The goal is to see how well Ruxolitinib works as part of the treatment process for this condition.

How Is the Trial Designed?

Group I: Ruxolitinib Not Eligible pre-HSCT Experimental Treatment 1 Intervention

* Ruxolitinib will be taken orally at a fixed dose twice every day after transplant * Dosing will be continuous, with a new cycle scheduled to start every 28 days. * There will be no break in dosing between cycles * Ruxolitinib can be administered with or without food.

Group II: Ruxolitinib Eligible pre-HSCT Experimental Treatment 1 Intervention

* Ruxolitinib will be taken orally at a fixed dose twice every day * Dosing will be continuous, with a new cycle scheduled to start every 28 days. * There will be no break in dosing between cycles * Ruxolitinib can be administered with or without food.

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/PMC4920055/

Efficacy and Safety of Ruxolitinib in the Treatment of Patients ... A total of 45.9% of patients in the ruxolitinib arm versus 5.3% of patients in the placebo arm had a ≥50% reduction in total symptom score (as assessed with the ...

2. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01471-z

Ten years of treatment with ruxolitinib for myelofibrosis Ruxolitinib has been shown to not only improve splenomegaly and the burdensome symptoms associated with MF but also to improve overall survival (OS).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39837682/

A Review of Real-World Experience With Ruxolitinib for ... Real-world evidence supports the effectiveness of ruxolitinib in improving splenomegaly and MF symptoms while significantly increasing overall survival.

4. ashpublications.org ashpublications.org/bloodneoplasia/article/2/2/100082/535814/Outcomes-for-ruxolitinib-only-versus-combination

Outcomes for ruxolitinib only versus combination with ... In this phase 2 trial, 44% of patients achieved either complete (CR) or partial responses (PR), including symptom, spleen size, hematologic, ...

5. jakafi.com jakafi.com/myelofibrosis/video-myelofibrosis-treatment-survival

What Long-Term Data Are Available for Jakafi? At 3 years, survival probability was estimated to be 70% for patients who started the trial taking Jakafi and 61% for those who started the trial taking a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4380721/

Efficacy, safety, and survival with ruxolitinib in patients with ... Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥3 anemia or thrombocytopenia with longer-term ruxolitinib ...

7. hcp.jakafi.com hcp.jakafi.com/myelofibrosis/safety

Safety Profile in Intermediate or High-Risk Myelofibrosis (MF) Jakafi® (ruxolitinib) adverse reactions · The most frequently observed adverse reactions were thrombocytopenia and anemia · Perform a pretreatment CBC, and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5060023/

Safety and efficacy of ruxolitinib in an open ... Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1 ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6573

Efficacy and safety of ruxolitinib in patients with lower risk ... By week 48, 26 (65.0%) patients achieved a ≥ 50% decrease in palpable spleen length. 32 (80.0%) patients achieved a ≥ 50% reduction from ...