Ruxolitinib for Aplastic Anemia

Overseen By Rachel B. Salit, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Must be taking: JAK inhibitors

Disqualifiers: Myocardial infarction, 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: 2

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of ruxolitinib in preventing graft versus host disease (GVHD), a common complication after bone marrow or stem cell transplants, in patients with acquired aplastic anemia. Aplastic anemia occurs when the bone marrow fails to produce enough blood cells, leading to frequent infections, fatigue, and bleeding. The study targets individuals over 40 or those aged 18-40 who encounter difficulties with standard treatments and are potential candidates for stem cell transplants. Participants should not have severe liver disease or a history of certain heart or clotting events. As a Phase 2 trial, this research measures 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that ruxolitinib, a type of medication, is generally well-tolerated by patients. Studies indicate that it can effectively lower the risk of graft-versus-host disease (GVHD) after a bone marrow or stem cell transplant. One study found that patients taking ruxolitinib had better outcomes, with fewer transplant-related complications, compared to those who did not take it.

Long-term safety data suggest that ruxolitinib remains effective over time. About three years after starting the medication, 78% of patients were still alive, indicating good survival rates. However, some side effects exist. The most common is a decrease in hemoglobin levels, leading to anemia in about 2.7% of people.

Overall, ruxolitinib has been used for over ten years and is approved for treating GVHD in other conditions, supporting its safety. This experience provides confidence in its use for preventing GVHD in patients with acquired aplastic anemia. ^{1 2 3 4 5}

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

Ruxolitinib is unique because it targets specific pathways involved in the immune system that are not addressed by traditional treatments for aplastic anemia, like immunosuppressive therapy or bone marrow transplants. Unlike these standard treatments, which can have broad and severe side effects, ruxolitinib specifically inhibits JAK1 and JAK2 enzymes, potentially offering a more targeted approach with fewer side effects. Researchers are excited about ruxolitinib because it represents a novel mechanism of action that could improve outcomes for patients who do not respond well to existing therapies.

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

Research has shown that ruxolitinib can help manage graft-versus-host disease (GVHD), a common issue after stem cell transplants. Studies found that adding ruxolitinib to standard GVHD prevention methods improved survival rates without GVHD and reduced transplant-related deaths compared to standard care alone. Additionally, early animal research suggested that ruxolitinib can prevent the immune system from attacking the bone marrow, potentially benefiting conditions like aplastic anemia. The drug blocks certain immune pathways, helping to control an overactive immune response. Although more research is needed, these findings indicate that ruxolitinib could benefit patients undergoing bone marrow or stem cell transplants. ^{3 6 7 8 9}

Who Is on the Research Team?

Rachel B. Salit, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for older adults with acquired aplastic anemia, a condition where the bone marrow doesn't produce enough blood cells. It's testing if adding ruxolitinib to standard treatment can prevent serious complications after a bone marrow or stem cell transplant.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My doctor thinks I could be a candidate for a stem cell transplant.

I am mostly able to care for myself.

Exclusion Criteria

I am allergic to JAK inhibitors or their ingredients.

Active or recent infection without infectious disease (ID) consult and approval

I have never been treated for tuberculosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Conditioning Regimen

Patients receive fludarabine and undergo total body irradiation before transplantation

4 days

Daily visits for treatment

Transplant

Patients undergo peripheral blood stem cell or bone marrow transplant

1 day

1 visit (in-person)

GVHD Prophylaxis

Patients receive cyclosporine, sirolimus, mycophenolate mofetil, and ruxolitinib to prevent GVHD

365 days

Regular visits for medication administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Periodic visits for monitoring and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study is examining a regimen that includes ruxolitinib, aiming to reduce graft versus host disease (GVHD) in patients receiving transplants. The effectiveness of this approach compared to standard GVHD prevention will be assessed.

How Is the Trial Designed?

Group I: Prevention (conditioning, transplant, GVHD prophylaxis) Experimental Treatment 15 Interventions

See Detailed Description.

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

Published Research Related to This Trial

Ruxolitinib is an effective treatment for patients with polycythaemia vera (PV) who do not respond well to hydroxyurea, showing superior results in reducing hematocrit and spleen size after 32 weeks in the phase III RESPONSE trial.

The drug is generally well tolerated, with manageable side effects like mild to moderate anemia and thrombocytopenia, making it a valuable option for PV patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: A Review in Polycythaemia Vera. McKeage, K.[2021]

In a phase 3b study involving 161 patients with polycythemia vera resistant or intolerant to hydroxyurea, ruxolitinib demonstrated a safety profile consistent with previous studies, with 37.9% of patients experiencing adverse events that required dose adjustments.

Ruxolitinib was effective, achieving hematocrit control in 45.3% of patients and significant spleen size reduction in 86.7%, indicating its potential as a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. Foltz, L., Pica, GM., Zerazhi, H., et al.[2021]

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]

In a phase 2 study involving 45 patients with myelofibrosis, a dose-escalation strategy for ruxolitinib starting at 10 mg twice daily helped reduce spleen size by an average of 17.3% and improved symptom severity by 45.6% after 24 weeks.

This approach also resulted in fewer severe hematological side effects, with only 20% of patients experiencing grade 3/4 anemia, suggesting that careful dose management can maintain treatment efficacy while minimizing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. Talpaz, M., Erickson-Viitanen, S., Hou, K., et al.[2021]

Ruxolitinib, the only approved therapy for myelofibrosis, showed a 51% response rate in reducing spleen size and a 42% response rate in alleviating symptoms in 45 patients treated off clinical studies, indicating its efficacy in advanced cases.

The treatment was effective even in patients previously treated with JAK inhibitors and could be safely combined with hypomethylating agents, suggesting potential for further exploration in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of ruxolitinib in an academic medical center in unselected patients with myeloproliferative neoplasms not on clinical study. Naqvi, K., Daver, N., Pemmaraju, N., et al.[2021]

Ruxolitinib is a well-absorbed tyrosine kinase inhibitor with 95% bioavailability, primarily metabolized in the liver, and its pharmacokinetics can vary based on factors like gender and body weight.

The drug's effectiveness can be influenced by liver and renal function, necessitating dose adjustments, and while model-informed precision dosing could enhance treatment personalization, more research is needed before it can be routinely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. Appeldoorn, TYJ., Munnink, THO., Morsink, LM., et al.[2023]

Ruxolitinib is currently the only approved treatment for myelofibrosis, but patients who stop taking it face poor outcomes, highlighting a significant need for alternative therapies.

New JAK inhibitors like fedratinib and momelotinib are being revisited, and combination therapies, such as adding azacitidine to ruxolitinib, show promise in improving treatment responses and managing side effects like cytopenias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Concepts of Treatment for Patients with Myelofibrosis. Bose, P., Alfayez, M., Verstovsek, S.[2023]

In a study of 462 patients with myelofibrosis, the safety profile of ruxolitinib was found to be comparable between new and prevalent users, with common adverse drug reactions including thrombocytopenia and anaemia.

Patients who switched to ruxolitinib experienced higher rates of bleeding events and serious infections, while the incidence of second primary malignancies was notably higher in those who were already using ruxolitinib, supporting its long-term use despite these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis. Barraco, F., Greil, R., Herbrecht, R., et al.[2021]

Ruxolitinib is shown to be safe and effective for treating myelofibrosis in Japanese patients, with 86.3% of the 51 participants completing the 24-week study and no deaths reported.

At 24 weeks, 30% of patients had significant reductions in spleen size, and there were notable improvements in symptoms and quality of life, even among those with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. Komatsu, N., Kirito, K., Shimoda, K., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11063833/

Efficacy of combined low-dose ruxolitinib and cyclosporine ... Using low-dose RUX or CsA monotherapy as controls, we found that RUX and CsA combined therapy significantly improved WBC, NEU, RBC, and PLT 2 weeks after BMF ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1323.1/529280/Trial-in-Progress-A-Phase-I-II-Study-of-the-JAK1-2

Trial in Progress: A Phase I/II Study of the JAK1/2 Inhibitor ... Use of ruxolitinib in pre-clinical data in a murine model of immune BMF achieved effective count recovery, suppressed activated T-cells ...

3. nature.com nature.com/articles/s41409-024-02266-7

Addition of ruxolitinib to standard graft-versus-host disease ... The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%).

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497122013076

Efficacy of JAK1/2 inhibition in murine immune bone ... Ruxolitinib prophylaxis prevents and ruxolitinib therapy treats murine immune aplastic anemia. •. Ruxolitinib inhibits T-cell infiltration ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06752694?term=AREA%5BConditionSearch%5D(%22Aplastic%20Anemia%22)&rank=10

Study Details | NCT06752694 | Ruxolitinib Based GVHD ... The current study aims to assess whether adding ruxolitinib to a standard GVHD prevention regimen may reduce the risk of Grade II-IV acute and chronic GVHD ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12490404/

Long-term safety and effectiveness of ruxolitinib in patients ... At Week 144 (Day 1008), the Kaplan – Meier estimated overall survival rate was 78% in the ruxolitinib arm, 61% in the intent-to-treat control ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124110920

A Phase I/II Study of the JAK1/2 Inhibitor Ruxolitinib for ... The primary endpoints are: (a) the primary safety endpoint will be number of participants who complete a full course of ruxolitinib without ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35661

Ten years of experience with ruxolitinib since approval for ... The most frequent AEs in the ruxolitinib postmarketing data overall were related to low hemoglobin (anemia, 2.7%; hemoglobin decreased, 2.2%), ...

9. ashpublications.org ashpublications.org/blood/article/141/1/72/486676/Efficacy-of-JAK1-2-inhibition-in-murine-immune

Efficacy of JAK1/2 inhibition in murine immune bone marrow ... Ruxolitinib prophylaxis prevents and ruxolitinib therapy treats murine immune aplastic anemia. Ruxolitinib inhibits T-cell infiltration and ...