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

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.

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.

What data supports the effectiveness of the drug Ruxolitinib for treating myelofibrosis?

Ruxolitinib has been shown to reduce spleen size and improve symptoms in patients with myelofibrosis, even in those with low platelet counts. It has also been associated with a high rate of successful transplantation when used before stem cell transplants, although its long-term effects and optimal use around the time of transplant are still being studied. ^{1 2 3 4 5}

Is ruxolitinib generally safe for humans?

Ruxolitinib has been studied in a large number of patients with myelofibrosis, and the most common side effects are anemia (low red blood cell count) and thrombocytopenia (low platelet count), which rarely lead to stopping the treatment. Other side effects, like infections, are usually mild. Overall, the safety profile of ruxolitinib is consistent with previous studies, and no new safety concerns have been identified. ^{1 2 4 6 7}

How is the drug Ruxolitinib unique in treating myelofibrosis?

Ruxolitinib is unique because it is an oral medication that specifically inhibits JAK1 and JAK2 enzymes, which are involved in the development of myelofibrosis. It is particularly notable for its ability to reduce spleen size and improve symptoms, and it is being explored for use around the time of stem cell transplantation, although its effects in this context are not yet fully understood. ^{1 2 3 4 8}

Research Team

Rachel B. Salit

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

How we manage JAK inhibition in allogeneic transplantation for myelofibrosis. [2015]

3. Brazil 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. [2021]

4. England 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups. [2022]

6. United States 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]