Peritransplant Ruxolitinib for Myelofibrosis

Overseen By Rachel B. Salit

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must be taking: JAK inhibitors

Disqualifiers: Renal impairment, Hepatic impairment, HIV, 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

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ruxolitinib (also known as Jakafi, Jakavi, or Opzelura) can prevent complications after a stem cell transplant in people with myelofibrosis, a bone marrow disorder. Stem cell transplants can sometimes cause graft versus host disease, where donor cells attack the patient's body. Ruxolitinib might reduce this risk and improve overall outcomes. People with primary or secondary myelofibrosis who are considering a stem cell transplant and experiencing symptoms like night sweats and weight loss might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you must be willing to start taking ruxolitinib and continue it for a specified period around the transplant.

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

Research shows that ruxolitinib is generally well-tolerated by patients. Studies have found that the most common side effects involve changes in blood counts, such as anemia (low red blood cell count) and thrombocytopenia (low platelet count). These side effects typically do not worsen over time with continued treatment.

Ruxolitinib has been used for many years to treat myelofibrosis and is known to help reduce symptoms like an enlarged spleen and improve overall survival. While some side effects occur, most patients find the treatment manageable. Prospective trial participants can rely on these findings to understand its safety based on real-world and study data. ^{1 2 3 4 5}

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

Researchers are excited about ruxolitinib for myelofibrosis because it targets a specific pathway called the JAK-STAT pathway, which is often overactive in this condition. This action helps to reduce inflammation and abnormal cell growth more effectively than traditional treatments, which typically focus on symptom management. Additionally, ruxolitinib has shown promise in improving spleen size and overall quality of life for patients, offering a potential new angle for treatment beyond the current standard therapies like hydroxyurea and interferon.

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 by reducing symptoms such as an enlarged spleen, night sweats, and weight loss. One study found that 45.9% of patients taking ruxolitinib experienced at least a 50% reduction in symptoms, compared to only 5.3% of those on a placebo. It has also improved overall survival rates, with long-term data suggesting better outcomes for patients. By reducing inflammation, ruxolitinib may lower the risk and severity of graft versus host disease, a common issue after stem cell transplants. This drug shows promise in enhancing the quality of life for people with myelofibrosis. ^{1 2 6 7 8}

Who Is on the Research Team?

Rachel B. Salit

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults over 18 with primary or secondary myelofibrosis, classified as intermediate-1, -2, or high-risk. Participants must have used ruxolitinib for at least 8 weeks before the transplant and be able to continue post-transplant. They should not have severe kidney or liver problems, uncontrolled infections, HIV, or be pregnant. A suitable stem cell donor is required.

Inclusion Criteria

I might be a candidate for a bone marrow transplant.

I have been on ruxolitinib for at least 8 weeks and can continue it for 9 months after my transplant.

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

Exclusion Criteria

I have an infection that is not under control.

Known HIV positivity

I do not have any uncontrolled infections.

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 starting 8 weeks prior to HSCT and continuing until approximately 14 days prior to conditioning regimen

8 weeks

Conditioning

Participants receive either myeloablative or reduced intensity conditioning regimens before HSCT

8 days

Transplant

Participants undergo hematopoietic stem cell transplantation (HSCT) on day 0

1 day

GVHD Prophylaxis

Participants receive ruxolitinib and other medications to prevent graft versus host disease post-transplant

9-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests if ruxolitinib given before, during, and after a stem cell transplant can prevent graft versus host disease and improve outcomes in myelofibrosis patients. It involves chemotherapy drugs like Melphalan and Fludarabine followed by transplantation of donor stem cells.

How Is the Trial Designed?

Group I: Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis) Experimental Treatment 15 Interventions

See detailed description.

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?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Published Research Related to This Trial

Ruxolitinib, a JAK 1/2 inhibitor, has shown benefits in treating myelofibrosis by reducing spleen size and improving symptoms, but its use around the time of hematopoietic stem cell transplantation (HCT) poses challenges such as unpredictable responses and potential cytokine storms upon discontinuation.

There is a need for more research to establish the best timing and protocols for using JAK inhibitors like ruxolitinib in HCT settings to improve patient outcomes, including engraftment and survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How we manage JAK inhibition in allogeneic transplantation for myelofibrosis. Ballinger, TJ., Savani, BN., Gupta, V., et al.[2015]

Ruxolitinib, an oral JAK1/2 inhibitor, is effective in reducing spleen size and symptom burden in patients with intermediate and high-risk myelofibrosis, making it a valuable treatment option before hematopoietic stem cell transplantation (HSCT).

The impact of ruxolitinib on HSCT outcomes is not well understood, and there is significant variability in how it is used in patients transitioning to HSCT, highlighting the need for more research to guide treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. Ibrahim, U., Petrone, GEM., Mascarenhas, J., et al.[2021]

In a study of 219 patients with myelofibrosis, ruxolitinib demonstrated a significant efficacy advantage over the best available therapy, with 28% of patients achieving at least a 35% reduction in spleen volume at 48 weeks, compared to 0% in the control group.

Ruxolitinib not only reduced spleen size but also improved overall quality of life and disease symptoms, with manageable side effects, primarily hematologic issues like thrombocytopenia and anemia, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. Harrison, C., Kiladjian, JJ., Al-Ali, HK., et al.[2022]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a phase 2 trial involving 51 patients with myelofibrosis who were intolerant to ruxolitinib, 43.2% of those treated with the novel JAK inhibitor jaktinib showed a significant reduction in spleen volume after 24 weeks.

Jaktinib also improved symptoms related to myelofibrosis, with 61.8% of patients experiencing a notable decrease in total symptom scores, although it was associated with some serious adverse events, including anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhou, H., Duan, M., et al.[2023]

In a study of 104 patients with intermediate- and high-risk myelofibrosis, ruxolitinib demonstrated significant efficacy, with over 62% of patients showing a reduction in spleen size after 24 weeks, and high survival rates at 48 weeks (91% progression-free survival).

While ruxolitinib was effective, it was associated with notable safety concerns, including a high incidence of adverse events (62.5% of patients experienced serious AEs) and a 19.2% occurrence of second malignancies, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. Tavares, R., Souza, CA., Paley, C., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, was evaluated in a large phase 3b study (N = 2233) for treating myelofibrosis, including patients with low platelet counts, showing significant reductions in spleen size and symptoms.

The safety profile of ruxolitinib was consistent with previous studies, with common adverse events like anemia and thrombocytopenia, but these rarely led to treatment discontinuation, indicating it is a viable option for patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Al-Ali, HK., Griesshammer, M., Foltz, L., et al.[2021]

In a phase 2 trial involving 76 myelofibrosis patients, a short course of ruxolitinib before transplantation led to a high transplantation rate of 92%, with 31% achieving a partial response prior to the procedure.

One-year disease-free survival (DFS) after transplantation was 55%, with significantly better outcomes for patients receiving HLA-matched sibling donor transplants (83% DFS) compared to those with unrelated donors (40% for HLA-matched and 34% for mismatched).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups. Robin, M., Porcher, R., Orvain, C., et al.[2022]

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. 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 ...

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. 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. 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 ...

8. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)02465-0/fulltext

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.