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

Trial Summary

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.

What data supports the effectiveness of the drug Ruxolitinib for treating aplastic anemia?

Research shows that Ruxolitinib, a drug that blocks certain proteins involved in immune responses, has been effective in animal models of aplastic anemia by reducing harmful immune cell activity and protecting blood-forming cells. This suggests potential benefits for human patients with similar conditions. ^{1 2 3 4 5}

Is Ruxolitinib generally safe for humans?

Ruxolitinib has been studied for various conditions, and common side effects include anemia (low red blood cell count) and thrombocytopenia (low platelet count). Some patients may experience headaches, diarrhea, or infections, and there is a risk of more serious issues like bleeding or second primary cancers. However, it is generally considered safe for long-term use in conditions like myelofibrosis and polycythemia vera, with careful monitoring. ^{3 6 7 8 9}

How does the drug Ruxolitinib differ from other treatments for aplastic anemia?

Ruxolitinib is unique because it targets the JAK-STAT pathway, which helps reduce the activity of harmful T-cells that destroy bone marrow cells in aplastic anemia. Unlike traditional treatments like stem cell transplantation or immunosuppression, Ruxolitinib is an oral medication that can be administered as a food additive, potentially offering a less invasive option. ^{2 3 5 10 11}

What is the purpose of this trial?

This phase II trial tests how well a ruxolitinib-based graft versus host disease (GVHD) prevention (prophylaxis) regimen works before, during, and after bone marrow/stem cell transplantation (hematopoietic cell transplantation \[HCT\]) in patients with acquired aplastic anemia. Acquired aplastic anemia (AA) is a condition in which the bone marrow is unable to produce blood cells. Affected patients typically present with infections due to abnormally low number of neutrophils, bleeding due to low platelet count, and/or fatigue due to a lower-than-normal number of red blood cells (anemia). Its incidence varies with age, occurring most frequently in patients aged 2-5 years, 20-25 years, and 55 years and older. Treatment of AA includes either immunosuppressive therapy (IST) or bone marrow/stem cell transplantation (HCT) with first-line therapy in younger adults often being HCT, while adults over 40 still frequently trial IST first due to the morbidity and mortality concerns with HCT. GVHD is a common complication after donor stem cell transplantation, resulting from donor immune cells recognizing recipients' cells and attacking them. Ruxolitinib, a drug in a class of oral medications called JAK inhibitors has been approved for the treatment of acute and chronic GVHD. It has also been shown to decrease GVHD when used in the prevention setting in patients with myelofibrosis. 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 after bone marrow/stem cell transplantation in older patients with acquired aplastic anemia.

Research Team

Rachel B. Salit, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. [2021]

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

Efficacy of JAK1/2 inhibition in murine immune bone marrow failure. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Ruxolitinib. [2021]

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

Clinical use of ruxolitinib in an academic medical center in unselected patients with myeloproliferative neoplasms not on clinical study. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. [2023]

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Hypoxemic Respiratory Failure Following Ruxolitinib Discontinuation in Allogeneic Hematopoietic Cell Transplantation Recipients. [2021]

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

New Concepts of Treatment for Patients with Myelofibrosis. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Ruxolitinib: A Review in Polycythaemia Vera. [2021]