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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Ruxolitinib Phosphate for reducing fatigue in patients with chronic lymphocytic leukemia?

Ruxolitinib has shown effectiveness in improving symptoms and quality of life in patients with myelofibrosis, a condition with similar symptom burdens, by reducing spleen size and symptom burden. This suggests it may help with symptom control in chronic lymphocytic leukemia as well. ^{1 2 3 4 5}

Is Ruxolitinib Phosphate generally safe for humans?

Ruxolitinib Phosphate, also known as Jakafi or Jakavi, has been studied for conditions like myelofibrosis and is generally well tolerated, but it can cause side effects like anemia (low red blood cell count) and thrombocytopenia (low platelet count). There have been rare cases of serious infections, such as JC virus meningitis, so monitoring is important. ^{3 6 7 8 9}

How is the drug Ruxolitinib Phosphate unique for treating chronic lymphocytic leukemia fatigue?

Ruxolitinib Phosphate is unique because it is an oral drug that specifically inhibits JAK1 and JAK2 enzymes, which are involved in the JAK-STAT pathway, a signaling pathway that can affect immune function and inflammation. This mechanism is different from other treatments for chronic lymphocytic leukemia, which may not target these specific enzymes. ^{2 3 10 11 12}

What is the purpose of this trial?

This trial studies how well ruxolitinib phosphate works in reducing fatigue in patients with chronic lymphocytic leukemia. The medication blocks a protein that helps cancer cells grow, which might also help with tiredness and other symptoms. Patients take the medication regularly unless their disease gets worse or they experience severe side effects.

Research Team

Alessandra Ferrajoli, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 am able to care for myself and perform daily activities.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Ruxolitinib. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]

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

Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. [2021]

5. United States 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. [2022]

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

Fatal ruxolitinib-related JC virus meningitis. [2021]

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

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis. [2021]

8. 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]

9. Italy pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. [2021]