INCB57643 + Ruxolitinib for Myelofibrosis

Overseen By Mahesh Swaminathan, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: BET inhibitors, JAK inhibitors

Disqualifiers: Splenectomy, Active infections, Liver cirrhosis, 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: Unknown

Duration: 24 weeks

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, systemic anticancer treatments other than hydroxyurea and anagrelide must be stopped at least 2 weeks before starting the study drugs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Ruxolitinib for treating myelofibrosis?

Ruxolitinib, a drug that blocks specific proteins involved in myelofibrosis, has been shown to reduce spleen size and improve symptoms in many patients with this condition. It was the first approved treatment for myelofibrosis and remains a standard of care, with evidence from clinical trials and real-world studies supporting its benefits. ^{1 2 3 4 5}

Is the combination of INCB57643 and Ruxolitinib safe for humans?

Ruxolitinib, also known as Jakafi or Jakavi, has been used for over a decade to treat myelofibrosis and is generally considered safe, though it can cause side effects like anemia (low red blood cell count) and thrombocytopenia (low platelet count). These side effects are usually manageable and rarely lead to stopping the treatment. ^{1 3 6 7 8}

How does the drug INCB57643 + Ruxolitinib differ from other treatments for myelofibrosis?

The combination of INCB57643 with Ruxolitinib is unique because Ruxolitinib is a potent oral inhibitor targeting JAK1 and JAK2, which are involved in the disease process of myelofibrosis, and it is already known to reduce spleen size and improve symptoms. The addition of INCB57643 may offer a novel approach, potentially enhancing the effects of Ruxolitinib, although specific details about INCB57643's role are not provided in the available research. ^{1 5 9 10 11}

What is the purpose of this trial?

To assess INCB05643 + ruxolitinib JAKi-naive patients with myelofibrosis

Research Team

Mahesh Swaminathan, MBBS

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

This trial is for patients who have primary myelofibrosis or myelofibrosis and haven't been treated with JAK inhibitors before. Specific inclusion and exclusion criteria details are not provided, but typically these would outline the health status required to participate.

Inclusion Criteria

Agree to use highly effective contraceptive methods

Written informed consent required

Life expectancy of more than 24 weeks

Exclusion Criteria

I have had my spleen removed.

I have been treated with a JAK inhibitor like ruxolitinib.

I do not have an active or chronic infection with TB, HIV, Hepatitis B, or Hepatitis C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCB57643 in combination with Ruxolitinib for 24 weeks to evaluate splenic response rate

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for adverse events and overall response rate through study completion

1 year

Treatment Details

Interventions

• INCB57643
• Ruxolitinib

Trial Overview The study is testing a combination of two drugs: INCB57643, which is a BET inhibitor, and Ruxolitinib. The goal is to see how effective this combo is for patients who have never taken JAK inhibitors.

Participant Groups

Group I: INCB+ R Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

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]

Ruxolitinib, the first approved treatment for myelofibrosis (MF), has shown significant improvements in spleen size and related symptoms in patients, based on results from Phase I/II and Phase III clinical trials involving direct comparisons to placebo and best available therapy.

While ruxolitinib is effective, it can cause side effects like cytopenias, which can be managed with dose adjustments, and there have been rare cases of infections related to immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ruxolitinib for myelofibrosis. Santos, FP., 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, an oral JAK1 and JAK2 inhibitor, has transformed the treatment of myelofibrosis (MF) since its approval, demonstrating significant clinical benefits in patients as shown in the phase 3 COMFORT-I/II trials.

Over the past 10 years, extensive research on ruxolitinib has enhanced the understanding of MF and its management, paving the way for future combination therapies to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years after ruxolitinib approval for myelofibrosis: a review of clinical efficacy. Pemmaraju, N., Bose, P., Rampal, R., et al.[2023]

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 study of 219 patients with myelofibrosis, ruxolitinib demonstrated a significant efficacy advantage over the best available therapy, with 28% of patients achieving at least a 35% reduction in spleen volume at 48 weeks, compared to 0% in the control group.

Ruxolitinib not only reduced spleen size but also improved overall quality of life and disease symptoms, with manageable side effects, primarily hematologic issues like thrombocytopenia and anemia, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. Harrison, C., Kiladjian, JJ., Al-Ali, HK., et al.[2022]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been the standard treatment for intermediate or high-risk myelofibrosis (MF) since its FDA approval in 2011, demonstrating significant efficacy in improving patient outcomes based on data from the phase 3 COMFORT trials.

The review highlights the importance of dose optimization and management of common side effects, such as anemia and thrombocytopenia, to maximize the safety and clinical benefits of ruxolitinib, supported by findings from subsequent trials like JUMP, ROBUST, EXPAND, and REALISE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. Verstovsek, S., Mesa, RA., Livingston, RA., 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]

In a study of 104 patients with intermediate- and high-risk myelofibrosis, ruxolitinib demonstrated significant efficacy, with over 62% of patients showing a reduction in spleen size after 24 weeks, and high survival rates at 48 weeks (91% progression-free survival).

While ruxolitinib was effective, it was associated with notable safety concerns, including a high incidence of adverse events (62.5% of patients experienced serious AEs) and a 19.2% occurrence of second malignancies, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. Tavares, R., Souza, CA., Paley, C., et al.[2021]

Ruxolitinib is an effective oral JAK1 and JAK2 inhibitor that has been shown to significantly reduce spleen size and improve symptoms in patients with myelofibrosis (MF), based on randomized phase III studies.

The treatment is generally well-tolerated, with manageable side effects like anemia and thrombocytopenia, leading to its approval by the FDA for intermediate or high-risk myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. Mascarenhas, J., Mughal, TI., Verstovsek, S.[2021]

Ruxolitinib is an effective oral treatment for intermediate- or high-risk myelofibrosis, targeting JAK1 and JAK2 to reduce spleen size and improve symptoms, as demonstrated in Phase III trials with significant improvements in quality of life and overall survival.

The treatment has a manageable safety profile, with common side effects including anemia and thrombocytopenia, and requires dosage adjustments based on platelet counts, allowing for personalized patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. Swaim, SJ.[2021]

References

1. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of ruxolitinib for myelofibrosis. [2021]

3. 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]

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

Ten years after ruxolitinib approval for myelofibrosis: a review of clinical efficacy. [2023]

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

Ruxolitinib. [2021]

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

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]

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

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Brazil pubmed.ncbi.nlm.nih.gov

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. [2021]

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

Ruxolitinib for the treatment of primary myelofibrosis. [2021]