Ruxolitinib + Stem Cell Transplant for Myelofibrosis

Overseen By Uday Popat, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Uncontrolled infection, Active hepatitis, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 100 days

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if taking ruxolitinib (a medication for certain bone marrow disorders) and busulfan before a stem cell transplant can shrink the spleen and improve transplant success for individuals with myelofibrosis, a type of bone marrow disorder. Participants will undergo treatment for approximately 100 days, followed by a year of check-ups. Suitable candidates may include those diagnosed with myelofibrosis, who have an enlarged spleen, and a suitable stem cell donor. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ruxolitinib, the drug used in this study, is generally safe for people with myelofibrosis. The FDA has approved it for treating this condition, indicating it is well-tolerated by many patients. Studies have found that using ruxolitinib before and after a stem cell transplant can be safe, with low rates of graft-versus-host disease (GVHD), a possible complication after transplants.

Additionally, ruxolitinib improves symptoms and quality of life for myelofibrosis patients, which may lead to better outcomes after a stem cell transplant. The evidence suggests that this treatment combination is manageable for patients, with low risks of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ruxolitinib combined with allogeneic stem cell transplantation for treating myelofibrosis because it offers a unique approach compared to standard treatments. While current options often involve medications like hydroxyurea or JAK2 inhibitors alone to manage symptoms, Ruxolitinib targets the JAK pathway more effectively when used alongside stem cell transplants. This combination not only aims to control the disease more precisely but also holds the potential for a longer-lasting remission by replacing unhealthy bone marrow with healthy cells. This dual-action strategy could significantly improve outcomes for patients with myelofibrosis.

What evidence suggests that ruxolitinib and stem cell transplantation could be effective for myelofibrosis?

Research has shown that taking ruxolitinib before a stem cell transplant for myelofibrosis can lead to better outcomes. In this trial, participants will receive both ruxolitinib and an allogeneic stem cell transplant. Studies have found that patients who used ruxolitinib before their transplant lived longer and experienced fewer complications. This medicine helps shrink the spleen and ease symptoms, potentially making the transplant more successful. Other research suggests that ruxolitinib does not harm the transplant's success and may even improve quality of life. Overall, using ruxolitinib with a stem cell transplant is a promising approach to treating myelofibrosis. ^{3 5 6 7 8}

Who Is on the Research Team?

Uday R. Popat

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for myelofibrosis patients with an enlarged spleen. Participants should be eligible for a stem cell transplant and able to take medications like ruxolitinib and busulfan. Specific eligibility details are not provided, but typically include age range, overall health status, and disease stage.

Inclusion Criteria

Able to provide written consent

I have a donor who is a perfect match for my transplant.

I have been diagnosed with Myelofibrosis and may have been treated with Jak inhibitors.

Exclusion Criteria

My kidney function, measured by creatinine clearance, is below 40ml/min.

Ejection fraction less than 40%

Corrected DLCO less than 50%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib and busulfan before undergoing an allogeneic stem cell transplantation

100 days

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and various outcomes such as graft function and survival

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Stem Cell Transplantation
• Ruxolitinib

Trial Overview The study tests if high doses of ruxolitinib followed by chemotherapy (busulfan) can shrink the spleen before a stem cell transplant in myelofibrosis patients. The goal is to see if this approach improves transplant success.

How Is the Trial Designed?

Group I: Ruxolitinib and Allogeneic Stem Cell Transplantation Experimental Treatment 10 Interventions

Participants will be asked to receive study drugs and a stem cell transplant and attend study visits, at which various tests and procedures will be performed. Participants are expected to receive treatment for about 100 days, followed by a year of follow-up.

Allogeneic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Stem Cell Transplantation for:

• Leukemia
• Myelodysplastic syndromes
• Myeloproliferative neoplasms
• Lymphoma
• Myelofibrosis

Approved in United States as Allogeneic Stem Cell Transplantation for:

• Leukemia
• Myelodysplastic syndromes
• Myeloproliferative neoplasms
• Lymphoma
• Myelofibrosis

Approved in Canada as Allogeneic Stem Cell Transplantation for:

• Leukemia
• Myelodysplastic syndromes
• Myeloproliferative neoplasms
• Lymphoma
• Myelofibrosis

Approved in Japan as Allogeneic Stem Cell Transplantation for:

• Leukemia
• Myelodysplastic syndromes
• Myeloproliferative neoplasms
• Lymphoma
• Myelofibrosis

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

Published Research Related to This Trial

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.

Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. Jaekel, N., Behre, G., Behning, A., et al.[2021]

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 159 myelofibrosis patients undergoing allogeneic stem cell transplantation, ruxolitinib pretreatment did not negatively impact key outcomes such as graft failure, engraftment, or non-relapse mortality, indicating its safety in this context.

There was a trend suggesting that patients who received ruxolitinib had a lower risk of relapse compared to those who did not, although this was not statistically significant, and overall survival rates remained similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. Shahnaz Syed Abd Kadir, S., Christopeit, M., Wulf, G., et al.[2021]

In a study of 16 patients with refractory relapsed FLT3-positive acute myeloid leukemia, sorafenib as salvage therapy led to a complete remission in 13 patients, demonstrating its efficacy both before and after allogeneic hematopoietic stem cell transplantation.

The 2-year overall survival rate was 75%, and the disease-free survival rate was 50.5%, indicating that sorafenib can significantly improve survival outcomes, although it was associated with a higher incidence of skin rash post-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sorafenib as salvage therapy in refractory relapsed acute myeloid leukemia with positive FLT3 mutation]. Zhang, Y., Xuan, L., Fan, Z., et al.[2023]

In a phase 3 trial involving 202 patients with FLT3-ITD acute myeloid leukaemia, sorafenib maintenance post-transplantation significantly reduced the 1-year cumulative incidence of relapse to 7.0% compared to 24.5% in the control group, indicating its efficacy in preventing relapse after allogeneic stem-cell transplantation.

The treatment was well tolerated, with no treatment-related deaths reported, and the most common adverse events were similar between the sorafenib and control groups, suggesting that sorafenib maintenance is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Xuan, L., Wang, Y., Huang, F., et al.[2021]

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative treatment for myelofibrosis (MF), but many patients are ineligible due to age and poor health.

Ruxolitinib, the first JAK inhibitor approved for advanced MF, improves symptoms and spleen size but does not significantly alter the disease's progression, highlighting the need for further research on its effects during the peritransplant period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era? Tamari, R., Mughal, TI., Rondelli, D., et al.[2021]

A patient with FLT3-mutated acute myeloid leukemia (AML) experienced a relapse after allogeneic stem cell transplantation, which is typically linked to a poor survival rate.

The case highlights the potential effectiveness of sorafenib monotherapy in treating this type of relapse, particularly in a patient presenting with leukemia cutis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib for relapsed FLT3-ITD-positive acute myeloid leukemia postallogeneic stem cell transplantation presenting as leukemia cutis. Brodie, R., Langabeer, SE., Quinn, J., et al.[2023]

FLT3 gene mutations are found in 25-30% of acute myeloid leukemia (AML) cases, leading to poor prognosis, but advancements in treatment, including FLT3 inhibitors and improved transplant techniques, are enhancing patient outcomes.

The review highlights the need for standardized transplant strategies and post-transplant maintenance therapies, particularly the use of FLT3 inhibitors, to optimize treatment for AML patients with FLT3-internal tandem duplication mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3-internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bazarbachi, A., Bug, G., Baron, F., et al.[2023]

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]

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, a drug used to treat steroid-refractory acute graft-versus-host disease in allogeneic hematopoietic cell transplantation (HCT) recipients, can lead to acute hypoxemic respiratory failure upon discontinuation, as observed in three patients within three months of stopping the medication.

Reinitiating ruxolitinib along with systemic corticosteroids resulted in rapid clinical improvement for these patients, highlighting the need for careful management of ruxolitinib dosing and discontinuation to avoid serious respiratory complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxemic Respiratory Failure Following Ruxolitinib Discontinuation in Allogeneic Hematopoietic Cell Transplantation Recipients. Anandappa, AJ., Hobbs, GS., Dey, BR., et al.[2021]

Allogeneic hematopoietic stem-cell transplantation (HSCT) is still the only curative treatment for myelofibrosis, and its use has increased due to better patient selection and advancements in donor matching and supportive care.

The approval of the JAK inhibitor ruxolitinib has raised important questions about its role in the transplant setting, particularly regarding its use before transplantation and how it may affect patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic stem-cell transplantation for myelofibrosis. Lavi, N., Rowe, JM., Zuckerman, T.[2021]

Patients with acute myeloid leukemia (AML) who achieve a second complete remission (CR2) before undergoing allogeneic hematopoietic cell transplantation (HCT) have a significantly higher 5-year survival rate of 39% compared to only 18% for those in first relapse (Rel1) and 21% for those with primary induction failure (PIF).

The study suggests that while HCT is most beneficial for patients in CR2, it can still be a valuable option for selected patients in Rel1 or PIF, emphasizing the importance of patient characteristics such as cytogenetic risk and performance status in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission. Weisdorf, DJ., Millard, HR., Horowitz, MM., et al.[2022]

Citations

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Improved Outcomes in Myelofibrosis after Allogeneic Stem ... Improved outcomes in myelofibrosis after allogeneic stem-cell transplantation in the era of Ruxolitinib pretreatment and intensified conditioning regimen.

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JAK Inhibitors and Allogeneic Stem Cell Transplantation for ... The availability of Janus Kinase (JAK)1/2 inhibitors allows clinicians to provide symptom relief and improved quality of life of MF patients.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725014460

Adult Pre-Hematopoietic Cell Transplantation Ruxolitinib in ... ... allogeneic hematopoietic cell transplantation for myelofibrosis: role of ruxolitinib in improving survival outcomes. Biol Blood Marrow ...

5. nature.com nature.com/articles/s41375-021-01276-4

Impact of prior JAK-inhibitor therapy with ruxolitinib on ... RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6706301/

Impact of Ruxolitinib on Myelofibrosis Patients Post ... Ongoing studies further demonstrated improved allogeneic SCT outcomes in patients who were previously treated with ruxolitinib (Gupta et al, 2019). However, the ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025021354

Allogeneic Transplant Outcomes in Myelofibrosis in the Era ... Baseline risk was high: 91% intermediate or higher by MIPSS70-plus v2, and 73% had ≥grade 2 marrow fibrosis. Pre-transplant treatment included JAK inhibitors in ...

8. astctjournal.org astctjournal.org/article/S2666-6367(25)01446-0/abstract

Long-Term Outcomes of a Phase II Prospective Study Ruxolitinib (Rux), the first FDA-approved JAK inhibitor for the treatment of myelofibrosis (MF), was initially studied in patients who were ...