Ruxolitinib Phosphate for Chronic Lymphocytic Leukemia Fatigue

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Rifampin, St. John's wort

Disqualifiers: Pregnancy, HIV, Uncontrolled infection, 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

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ruxolitinib phosphate to determine if it can reduce fatigue in people with chronic lymphocytic leukemia (CLL). The drug blocks a protein that aids cancer cell growth and might also shrink lymph nodes and lower leukemia cells in the blood. This trial suits those diagnosed with CLL who experience significant fatigue and have not yet required treatment according to specific medical guidelines. Participants must have stopped CLL treatments at least 30 days before joining the study. 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?

You must stop taking all drugs used to treat chronic lymphocytic leukemia at least 30 days before starting the trial. If you are on any prohibited medications, you may need to stop them unless the investigator decides it's best for you to continue.

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

Research shows that ruxolitinib phosphate is generally well-tolerated by patients, with no unexpected safety issues identified. In earlier studies, only a few patients developed non-melanoma skin cancer, at a rate of 0.46 cases per 100 patient-years. This means that for every 100 people treated for a year, less than one person experienced this skin issue.

Furthermore, long-term research indicates that ruxolitinib is safe and effective for conditions like chronic graft-vs-host disease, where it has outperformed standard treatments over three years. This suggests the drug has a reliable safety record across different patient groups. Overall, while side effects can occur, they are usually manageable, and serious problems are rare. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ruxolitinib phosphate is unique because it targets the Janus kinase (JAK) pathway, which plays a crucial role in the inflammation and immune response associated with chronic lymphocytic leukemia (CLL) fatigue. Unlike standard treatments for CLL, which often focus on directly attacking cancer cells, ruxolitinib phosphate aims to alleviate one of the most debilitating symptoms—fatigue—by modulating immune system activity. This approach not only offers a potential new way to improve quality of life for CLL patients but also expands the possibilities for managing symptoms beyond traditional chemotherapy and targeted therapies. Researchers are excited about its potential to provide relief where current treatments might fall short.

What evidence suggests that ruxolitinib phosphate might be an effective treatment for chronic lymphocytic leukemia fatigue?

Studies have shown that ruxolitinib phosphate, the treatment tested in this trial, can significantly reduce tiredness in patients with chronic lymphocytic leukemia (CLL). This medication blocks a protein called Janus kinase (JAK), which is involved in cell growth and may help manage symptoms like tiredness. In previous research, patients noticed a clear decrease in their tiredness levels after taking ruxolitinib. The drug also helps shrink swollen lymph nodes and reduce the number of leukemia cells in the blood. Overall, ruxolitinib has shown promising results in improving the quality of life for people with CLL. ^{3 5 6 7 8}

Who Is on the Research Team?

Alessandra Ferrajoli, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with chronic lymphocytic leukemia who experience fatigue, have stable blood counts, and are not in immediate need of CLL treatment. They must understand the study and consent to participate. Pregnant or breastfeeding women, those with recent serious illnesses or infections, and individuals on certain medications are excluded.

Inclusion Criteria

I have been diagnosed with CLL but do not require treatment yet.

I am able to care for myself and perform daily activities.

I experience noticeable symptoms from my condition.

Exclusion Criteria

I needed blood transfusions due to low blood counts, not because of surgery.

I am not taking any medications that are not allowed in the study, except when approved by the study doctor.

Subjects of childbearing potential who are unwilling to take appropriate precautions (throughout the study from screening, including 30 days after discontinuation of the study drug) to avoid becoming pregnant or fathering a child

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib phosphate orally twice daily for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib Phosphate

Trial Overview The trial tests Ruxolitinib Phosphate's effectiveness in reducing fatigue associated with chronic lymphocytic leukemia by blocking a protein called JAK that cancer cells need to grow. It also evaluates changes in lymph node size and leukemia cell counts.

How Is the Trial Designed?

Group I: Supportive care (ruxolitinib phosphate) Experimental Treatment 2 Interventions

Patients receive ruxolitinib phosphate PO BID (approximately 12 hours apart) for up to 2 years in the absence of disease progression or unacceptable toxicity.

Ruxolitinib Phosphate is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Atopic dermatitis
• Vitiligo

Approved in European Union as Jakavi for:

• Myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ruxolitinib is an effective oral treatment for myelofibrosis, leading to significant reductions in spleen size and symptom burden for most patients, and may improve survival rates regardless of JAK2 V617F mutation status.

The main side effects of ruxolitinib include thrombocytopenia (low platelet count) and anemia, and its metabolism can be affected by other medications that inhibit the CYP3A4 enzyme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib. Becker, H., Engelhardt, M., von Bubnoff, N., et al.[2021]

Ruxolitinib is strongly recommended for patients with myelofibrosis to improve severe splenomegaly and systemic symptoms, particularly in those with specific risk scores and symptoms like severe itching or unexplained weight loss.

However, there is weak evidence supporting the use of ruxolitinib for improving survival, and these recommendations do not apply to patients eligible for allogeneic stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. Marchetti, M., Barosi, G., Cervantes, F., et al.[2021]

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

A 72-year-old man with myelofibrosis developed symptoms of meningitis, including fever and cognitive impairment, just 14 days after starting treatment with ruxolitinib, suggesting a potential link between the drug and JC virus meningitis.

The diagnosis was supported by positive JC virus PCR in the cerebrospinal fluid (CSF) and MRI findings, indicating that ruxolitinib may increase the risk of serious viral infections like JC virus meningitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal ruxolitinib-related JC virus meningitis. Ballesta, B., González, H., Martín, V., et al.[2021]

Ruxolitinib, a JAK1 and JAK2 inhibitor, has been shown to significantly improve symptoms and splenomegaly in patients with myelofibrosis, providing a survival advantage over placebo and best available therapy in Phase III clinical studies.

Monitoring blood counts and adjusting doses are crucial due to potential dose-dependent side effects, and discontinuing ruxolitinib can lead to a quick return of symptoms, highlighting the need for careful management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis. Arana Yi, C., Tam, CS., Verstovsek, S.[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 3-year follow-up of the COMFORT-II Trial involving 219 patients with myelofibrosis, ruxolitinib demonstrated sustained reductions in spleen size and improved quality of life, with 45% of patients remaining on treatment after 3 years.

Ruxolitinib was well tolerated, with manageable side effects like anemia and thrombocytopenia, and it was associated with longer overall survival compared to the best available therapy, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Cervantes, F., Vannucchi, AM., Kiladjian, JJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5356368/

Ruxolitinib for symptom control in patients with Chronic ... – Our study demonstrated that ruxolitinib significantly reduced the levels of fatigue and other disease-related symptoms in patients with CLL ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02131584/ruxolitinib-phosphate-in-reducing-fatigue-in-patients-with-chronic-lymphocytic-leukemia?activelyRecruiting=false&page=55&id=745&slug=chronic-lymphocytic-leukemia

Ruxolitinib Phosphate in Reducing Fatigue in Patients With ... This phase II trial studies how well ruxolitinib phosphate works in reducing fatigue in patients with chronic lymphocytic leukemia.

3. withpower.com withpower.com/trial/phase-3-fatigue-8-2014-3914d

Ruxolitinib Phosphate for Chronic Lymphocytic Leukemia ... This trial studies how well ruxolitinib phosphate works in reducing fatigue in patients with chronic lymphocytic leukemia. The medication blocks a protein ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03041636?term=Ruxolitinib&viewType=Table&rank=3&tab=results

Study Results | NCT03041636 | Ruxolitinib Phosphate in ... Patients receive ruxolitinib phosphate PO twice a daily (BID). Treatment continues for up to 3 years in the absence of disease progression or unacceptable ...

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

Ten years of experience with ruxolitinib since approval for ... This review covers ruxolitinib efficacy and safety data from clinical trials and real-world settings in the decade since ruxolitinib was ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03041636?term=RUXOLITINIB&rank=9

Ruxolitinib Phosphate in Treating Patients With Previously ... This phase II trial studies how well ruxolitinib phosphate works in treating patients with previously untreated chronic lymphocytic leukemia/small ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602646/

Clinical Review - Ruxolitinib (Jakavi) - NCBI - NIH According to the clinical experts consulted by CADTH, no unexpected safety concerns were observed with ruxolitinib. Go to: Introduction. Disease Background.

8. targetedonc.com targetedonc.com/view/long-term-reach3-data-confirm-ruxolitinib-s-efficacy-in-steroid-refractory-cgvhd

Long-Term REACH3 Data Confirm Ruxolitinib's Efficacy in ... Ruxolitinib shows sustained efficacy and safety in treating steroid-refractory chronic graft-vs-host disease, outperforming standard therapies over three years.