Ruxolitinib for Myelofibrosis

Overseen By Rachel Salit, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Must be taking: JAK inhibitors

Disqualifiers: HIV, Untreated TB, Recent MI, 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

Compensation: Varies

Number of Visits: 28

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding ruxolitinib, a medication that may halt harmful immune responses and cancer growth, to standard treatments can aid older patients with myelofibrosis or similar conditions during and after a stem cell transplant. The goal is to determine if this combination can prevent graft-versus-host disease (GVHD), where transplanted cells attack the body's own cells, and improve overall recovery. Patients dealing with myelofibrosis or related conditions who are candidates for a stem cell transplant might be suitable participants. As a Phase 2 trial, the research focuses on measuring 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 information does not specify if you need to stop taking your current medications. However, you must be willing to take ruxolitinib for at least 8 weeks before the transplant and continue it for up to 12 months after, followed by a 6-month taper.

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

Research has shown that ruxolitinib is generally well-tolerated by people with myelofibrosis (MF). Studies have identified common side effects, such as low blood cell counts, particularly anemia (low red blood cells) and thrombocytopenia (low platelets). These side effects can be managed and typically do not worsen significantly over time. For over ten years, ruxolitinib has been used to treat MF and has improved symptoms and increased survival rates. Although ruxolitinib affects blood cell counts, regular check-ups and adjustments can help manage these effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for myelofibrosis?

Ruxolitinib is unique because it targets the JAK1 and JAK2 pathways, which are often overactive in myelofibrosis, a rare bone marrow disorder. Unlike standard treatments that primarily manage symptoms, ruxolitinib directly tackles the underlying disease mechanism, potentially offering more comprehensive disease control. Researchers are excited about ruxolitinib because it can be used in combination with other therapies, like high-intensity or reduced-intensity conditioning regimens, which might enhance the overall treatment effectiveness and improve patient outcomes.

What evidence suggests that ruxolitinib might be an effective treatment for myelofibrosis?

Research has shown that ruxolitinib effectively treats myelofibrosis (MF). In one study, about 44% of patients with MF experienced either full or partial relief from symptoms, a reduction in spleen size, or improved blood counts. Another study found that ruxolitinib not only reduced spleen size and symptoms but also extended patients' lives. Additionally, finding the right dose of ruxolitinib has been linked to better results and manageable side effects for MF patients. In this trial, participants will receive ruxolitinib as part of their treatment regimen, which may help prevent graft versus host disease (GVHD) and improve outcomes for patients undergoing blood stem cell transplants. ^{3 6 7 8 9}

Who Is on the Research Team?

Rachel Salit, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for older patients with myelofibrosis or MDS/MPN overlap syndromes. Participants must be eligible for a stem cell transplant from a donor and able to receive medications like ruxolitinib, tacrolimus, and methotrexate.

Inclusion Criteria

* PART 1 JAK INHIBITOR ADMINISTRATION: Age 18-75 years

* Patients \> 75 must be considered an HCT candidate, meet all protocol criteria and have comorbidity score =\< 3 and Karnofsky performance status (KPS) \> or = to 90. Patients. \> 75 who do not meet these criteria may be presented at PCC for consensus exception

* PART 1 JAK INHIBITOR ADMINISTRATION: Disease criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Conditioning Treatment

Patients receive ruxolitinib or an alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning

8 weeks

Conditioning and Transplantation

Patients receive high or reduced intensity conditioning chemotherapy followed by stem cell infusion

Approximately 2 weeks

In-patient stay for conditioning and transplantation

Post-Transplant Treatment

Patients receive ruxolitinib and GVHD prophylaxis with tacrolimus and methotrexate

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Visits at days 28, 100, 180, 9 months, 1 year, 18 months, and 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Methotrexate
• Ruxolitinib

Trial Overview The study tests adding ruxolitinib to standard GVHD prevention in older patients undergoing donor stem cell transplants. It aims to see if this approach is safe and effective in preventing GVHD compared to the usual treatment without ruxolitinib.

How Is the Trial Designed?

Group I: Treatment (ruxolitinib) Experimental Treatment 14 Interventions

PART 1: Patients receive ruxolitinib or alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning. PART 2: Starting on day -4, patients receive ruxolitinib 5mg PO BID for 12 months then PO QD until 18 months. Patients receive high intensity conditioning with cyclophosphamide IV on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2 or reduced intensity conditioning with fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients receive stem cells infusion on day 0. Starting on day -3, patients receive tacrolimus IV over 1-2 hours or PO every 12 hours for at least 100 days. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Additionally, patients undergo urine sample collection, echocardiography, and pulmonary function testing prior to conditioning and blood sample collection, bone marrow biopsy and aspiration, and spleen ultrasound or CT throughout the study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

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/PMC12490404/

Long-term safety and effectiveness of ruxolitinib in patients ... After 6 months of ruxolitinib treatment, 26.2% of patients had a spleen response and 52.0% of patients had less symptoms. We could not calculate ...

2. 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, ...

3. 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).

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024024650

A Review of Real-World Experience With Ruxolitinib for ... Data from the COMFORT trials indicated that ruxolitinib treatment was associated with significantly longer OS compared with placebo or best available treatment.

5. curetoday.com curetoday.com/view/optimal-jakafi-dosing-associated-with-improved-outcomes-in-myelofibrosis

Optimal Jakafi Dosing Associated With Improved ... Optimal dosing of Jakafi (ruxolitinib) was associated with improved efficacy and manageable safety in patients with myelofibrosis, according to study findings.

6. 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 ...

7. 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 ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1786/529894/Comparing-the-Efficacy-and-Safety-of-Ruxolitinib

Comparing the Efficacy and Safety of Ruxolitinib in Patients ... Ruxolitinib is an effective treatment for patients with lower risk MF in the classification of MIPSS-70, MIPSS+V2.0, DIPSS-Plus, DIPSS≤2 and MYSEC-PM.

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 ...