Ruxolitinib for Chronic Myelomonocytic Leukemia

Recruiting at 5 trial locations

Overseen By Meagan Horton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Cytotoxic agents, GM-CSF

Disqualifiers: Metastatic malignancy, Serious illness, 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: 1

Duration: 16 weeks

29 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug (ruxolitinib) can improve outcomes of patients with CMML.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain treatments like cytotoxic chemotherapy or experimental agents for CMML within 28 days before starting the study drug. Some medications like stable doses of erythropoietin stimulating agents or corticosteroids are allowed if they were started before the trial.

What data supports the effectiveness of the drug Ruxolitinib for treating chronic myelomonocytic leukemia?

Research shows that Ruxolitinib, a drug that blocks certain proteins (JAK1 and JAK2) involved in cell growth, has been effective in treating chronic myelomonocytic leukemia by inducing positive responses in patients. Additionally, Ruxolitinib is already used to treat myelofibrosis, another blood disorder, where it helps reduce symptoms and spleen size. ^{1 2 3 4 5}

Is ruxolitinib generally safe for humans?

Ruxolitinib has been studied in various conditions, and common side effects include anemia (low red blood cell count) and thrombocytopenia (low platelet count), which are usually manageable and rarely lead to stopping the treatment. Infections and other non-blood-related side effects are generally mild. Overall, no new safety concerns have been identified in large studies. ^{1 6 7 8 9}

How is the drug Ruxolitinib unique for treating chronic myelomonocytic leukemia?

Ruxolitinib is unique because it targets JAK1 and JAK2 proteins, which are involved in the growth of certain blood cells, and it has shown promising results in reducing symptoms in patients with chronic myelomonocytic leukemia, a condition with limited treatment options. ^{1 2 3 10 11}

Research Team

Eric Padron, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

Adults diagnosed with Chronic Myelomonocytic Leukemia (CMML) who can attend scheduled visits, provide bone marrow samples, and have a life expectancy over 3 months. They must not be pregnant or breastfeeding, agree to use contraception if of childbearing potential, and have an ECOG score of 0-2. Excluded are those with certain blood abnormalities, recent chemotherapy or experimental treatments, uncontrolled illnesses like heart failure or severe infections.

Inclusion Criteria

I have a large spleen and/or severe symptoms from my blood disorder.

I agree to use two forms of birth control or abstain from sex during the study.

I have been diagnosed with Chronic Myelomonocytic Leukemia.

Exclusion Criteria

Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study

I am using GM-CSF or have used G-CSF for infection due to low neutrophils.

I do not have any uncontrolled illnesses that could affect my study participation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral Ruxolitinib, starting with 20 mg at the first visit, followed by 40 mg daily for 16 weeks

16 weeks

1 initial visit (in-person), followed by self-administration

Follow-up

Participants are monitored monthly for safety and effectiveness after treatment

Monthly follow-up

Long-term monitoring

Participants are monitored every 6 months for AML transformation and other outcomes

Up to 40.3 months

Treatment Details

Interventions

• Ruxolitinib

Trial Overview The trial is testing Ruxolitinib's effectiveness in improving outcomes for patients with CMML. It involves taking the study drug under supervision to see if it helps manage symptoms better than current standard treatments.

Participant Groups

Group I: Ruxolitinib Experimental Treatment 1 Intervention

All patients will be given their first dose of oral Ruxolitinib, 20 mg at first scheduled visit. After that dose and on all other days patients will self-administer oral Ruxolitinib at a dose of 40 mg daily divided into two equal doses approximately 12 hours apart. Patients will be treated for a total of 16 weeks. After treatment, patients will be followed monthly.

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

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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 I clinical trial involving 20 patients with chronic myelomonocytic leukemia (CMML), ruxolitinib was found to be safe, with no dose-limiting toxicities and only one case of grade 3 thrombocytopenia, indicating a favorable safety profile for this treatment.

Ruxolitinib demonstrated promising efficacy, with a total response rate of 35% and significant improvements in symptoms and spleen size, particularly benefiting patients with disease-related symptoms, suggesting it warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). Padron, E., Dezern, A., Andrade-Campos, M., et al.[2021]

Chronic myelomonocytic leukemia (CMML) shows increased sensitivity of myeloid progenitors to granulocyte macrophage-colony stimulating factor, indicating a need for targeted therapies.

Ruxolitinib, a JAK1 and JAK2 inhibitor, has been demonstrated to induce objective responses in patients with CMML, suggesting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia. Solary, E.[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]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a real-world study of 928 patients with myelofibrosis, ruxolitinib (RUX) demonstrated significant efficacy, with 82.5% of JAKi-naïve patients experiencing rapid reductions in spleen size within one month, and 60% maintaining this response for 24 months.

Common adverse events included anemia (31.2%) and thrombocytopenia (28.6%), but no new safety concerns were identified, confirming RUX's safety profile in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world analysis of ruxolitinib in myelofibrosis: interim results focusing on patients who were naïve to JAK inhibitor therapy treated within the JAKoMo non-interventional, phase IV trial. Koschmieder, S., Isfort, S., Schulte, C., et al.[2023]

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]

Ruxolitinib, a JAK1/JAK2 inhibitor, was evaluated in a large phase 3b study (N = 2233) for treating myelofibrosis, including patients with low platelet counts, showing significant reductions in spleen size and symptoms.

The safety profile of ruxolitinib was consistent with previous studies, with common adverse events like anemia and thrombocytopenia, but these rarely led to treatment discontinuation, indicating it is a viable option for patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Al-Ali, HK., Griesshammer, M., Foltz, L., et al.[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 phase 3 study involving 222 patients with polycythemia vera, ruxolitinib significantly outperformed standard therapy, achieving hematocrit control in 60% of patients and a 35% reduction in spleen volume in 38% of patients, compared to only 20% and 1% respectively in the standard therapy group.

Ruxolitinib also led to a higher rate of complete hematologic remission (24% vs. 9%) and a greater reduction in total symptom scores (49% vs. 5%), while maintaining a manageable safety profile with low rates of severe anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Vannucchi, AM., Kiladjian, JJ., Griesshammer, M., et al.[2022]

Patients treated with ruxolitinib, a JAK inhibitor for myelofibrosis and polycythemia vera, have a significantly increased risk of developing Mycobacterium tuberculosis (MTB) and atypical mycobacterial infections (AMI), with reporting odds ratios of 9.2 and 8.3, respectively.

Out of the reported cases, 13.2% of patients with MTB and 34.8% with AMI died, highlighting the importance of screening for latent MTB before starting ruxolitinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. Anand, K., Burns, EA., Ensor, J., et al.[2021]

References

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

A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). [2021]

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

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia. [2021]

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

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

4. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Real-world analysis of ruxolitinib in myelofibrosis: interim results focusing on patients who were naïve to JAK inhibitor therapy treated within the JAKoMo non-interventional, phase IV trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. [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. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib versus standard therapy for the treatment of polycythemia vera. [2022]

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

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. [2021]

11. 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]