Ruxolitinib + Panobinostat for Myelofibrosis

Recruiting at 88 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Ruxolitinib, Panobinostat

Disqualifiers: Pregnancy, Nursing, Approved indication, 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: 12 years

279 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it seems you need to be already on ruxolitinib or a combination of ruxolitinib and panobinostat to participate.

What data supports the effectiveness of the drug combination of ruxolitinib and panobinostat for myelofibrosis?

The combination of ruxolitinib and panobinostat was found to be safe and tolerable in a small study, with 40% of patients showing clinical improvement, such as reduced spleen size or improved anemia. Ruxolitinib alone is already known to reduce symptoms and spleen size in myelofibrosis, and panobinostat has shown some activity in early trials, suggesting potential benefits when used together. ^{1 2 3 4 5}

Is the combination of ruxolitinib and panobinostat safe for treating myelofibrosis?

The combination of ruxolitinib and panobinostat has been found to be safe and tolerable in a phase I trial for myelofibrosis, with no dose-limiting side effects observed. Ruxolitinib alone has a known safety profile, with common side effects including low blood cell counts and infections, but it is generally considered safe for long-term use in myelofibrosis. ^{1 3 6 7 8}

How is the drug combination of ruxolitinib and panobinostat unique for treating myelofibrosis?

The combination of ruxolitinib and panobinostat is unique because it combines a JAK1/JAK2 inhibitor with a histone deacetylase inhibitor, potentially offering a synergistic effect that may improve outcomes in myelofibrosis patients compared to ruxolitinib alone. This approach aims to not only reduce symptoms and spleen size but also modify the disease course, which is a novel strategy in treating this condition. ^{1 2 3 9 10}

What is the purpose of this trial?

This is a long term safety study for patients that have been treated with either ruxolitinib or a combination of ruxolitinib with panobinostat, on a Novartis or Incyte sponsored study, who have been judged by the study Investigator to benefit from ongoing treatment.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for patients already enrolled in a Novartis or Incyte-sponsored study, receiving ruxolitinib alone or with panobinostat, and benefiting from it without progressive disease. They must have met all prior study requirements and shown compliance.

Inclusion Criteria

I am currently in a Novartis or Incyte study and meet all its requirements.

I am currently seeing positive results from my ruxolitinib treatment, alone or with panobinostat, and have followed all study requirements.

My condition hasn't worsened after treatment with ruxolitinib or its combination with panobinostat.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue receiving ruxolitinib monotherapy or ruxolitinib plus panobinostat as per their previous study regimen

12 years

Follow-up

Participants are monitored for safety and clinical benefit

12 years

Treatment Details

Interventions

• panobinostat
• ruxolitinib

Trial Overview The trial continues the use of ruxolitinib, either alone or combined with panobinostat, to assess long-term safety in treating conditions like Polycythemia Vera and Acute Myeloid Leukemia among others.

Participant Groups

Group I: Ruxolitinib monotherapy or ruxolitinib plus panobinostat in combination Experimental Treatment 2 Interventions

All participants will receive either ruxolitinib monotherapy or ruxolitinib in combination with panobinostat, at the same dose/schedule that they were taking in the parent study.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

The combination of ruxolitinib and panobinostat in a phase I trial involving 15 patients with myelofibrosis was found to be safe and tolerable, with no dose-limiting side effects observed.

40% of patients experienced clinical improvement after 6 cycles of treatment, indicating that this combination therapy may enhance treatment outcomes for myelofibrosis compared to ruxolitinib alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post--polycythemia vera/essential thrombocythemia myelofibrosis (post--PV/ET MF). Mascarenhas, J., Marcellino, BK., Lu, M., et al.[2021]

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]

In a double-blind trial involving 309 patients with intermediate-2 or high-risk myelofibrosis, ruxolitinib significantly reduced spleen volume by 35% or more in 41.9% of patients compared to only 0.7% in the placebo group, demonstrating its efficacy (P<0.001).

Ruxolitinib also improved overall survival, with a hazard ratio of 0.50 for death compared to placebo, while common side effects included anemia and thrombocytopenia, which were manageable and rarely led to discontinuation of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. Verstovsek, S., Mesa, RA., Gotlib, J., et al.[2022]

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 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, 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 study of 1752 myelofibrosis (MF) patients, the incidence of blast phase (BP) was found to be 2.5% per year, with higher rates (4.3% and 4.5%) in patients with severe anemia (CTCAE grade 3/4 and grade 2, respectively).

Among 273 MF patients treated with ruxolitinib (RUX), the BP incidence was similar at 2.89% per year, indicating that the risk of BP in anemic MF patients is significant regardless of RUX treatment, which is important for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of blast phase in myelofibrosis according to anemia severity. Mora, B., Maffioli, M., Rumi, E., et al.[2023]

Ruxolitinib, a targeted treatment for myelofibrosis, shows significant benefits in reducing spleen size and improving 5-year overall survival, especially when used in combination with other therapies like prednisone and thalidomide.

Ruxolitinib-based combination therapies generally result in fewer treatment-related adverse events compared to ruxolitinib alone, indicating improved safety and tolerability, although genetic testing prior to treatment is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to. Li, Y., Zhu, S., Liu, W., 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]

References

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

A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post--polycythemia vera/essential thrombocythemia myelofibrosis (post--PV/ET MF). [2021]

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

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

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

A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF). [2018]

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

A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. [2022]

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

Ruxolitinib. [2021]

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

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

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

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

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

Incidence of blast phase in myelofibrosis according to anemia severity. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to. [2021]

10. 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]