Ruxolitinib + Panobinostat for Myelofibrosis

Not currently recruiting at 112 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study the long-term safety of treatments for myelofibrosis, a rare bone marrow disorder that disrupts blood cell production. Participants will continue using either ruxolitinib (a JAK inhibitor) alone or combined with panobinostat (an HDAC inhibitor), maintaining the same dosage and schedule from a previous study. The trial is designed for those already benefiting from these treatments and who have shown no disease progression. Individuals currently part of a related study and doing well with these treatments might be a good fit. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved treatment benefits more patients.

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 is the safety track record for ruxolitinib and panobinostat?

Research has shown that both ruxolitinib alone and in combination with panobinostat have been generally safe in previous studies. Common side effects of ruxolitinib include anemia (low red blood cell count) and thrombocytopenia (low platelet levels), which can be managed effectively. Long-term use does not appear to worsen these conditions.

When combined with panobinostat, ruxolitinib remains safe, as studies have found. Only a few patients experience serious side effects that require dose adjustments. Past research has determined safe dosage levels. Although rare, some serious events like heart attacks have been reported.

Overall, these treatment options are generally well-tolerated, and participants in these trials usually continue treatment without major problems. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for myelofibrosis, which usually involve single-agent therapies, this approach combines ruxolitinib with panobinostat. Ruxolitinib targets the JAK2 pathway, which is crucial in managing symptoms and reducing spleen size, while panobinostat is a histone deacetylase inhibitor that may enhance the effectiveness of ruxolitinib by modifying gene expression. Researchers are excited about this combination because it has the potential to provide a more comprehensive treatment by not only alleviating symptoms but also addressing the underlying disease mechanisms more effectively than current options.

What is the effectiveness track record for ruxolitinib and panobinostat in treating myelofibrosis?

Research has shown that ruxolitinib effectively treats myelofibrosis, a type of bone marrow cancer. It helps shrink the spleen, improve symptoms, and extend patients' lives. Real-world studies indicate that more than half of the patients experience a significant reduction in spleen size.

In this trial, participants will receive either ruxolitinib monotherapy or a combination of ruxolitinib and panobinostat. The combination of ruxolitinib with panobinostat has shown promising results, with clinical improvement observed in 40% of patients. Early studies suggest that this combination works well together, potentially making it more effective than ruxolitinib alone. ^{2 3 5 6 7}

Who Is on the Research Team?

Novartis Pharma, A.G

Principal Investigator

Novartis Pharma, A.G.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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, 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 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 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 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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39837682/

A Review of Real-World Experience With Ruxolitinib for ...

Real-world evidence supports the effectiveness of ruxolitinib in improving splenomegaly and MF symptoms while significantly increasing overall survival.

2.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)02465-0/fulltext

A Review of Real-World Experience With Ruxolitinib for ...

Real-world evidence supports the effectiveness of ruxolitinib in improving splenomegaly and MF symptoms while significantly increasing overall survival.

3.

jhoonline.biomedcentral.com

jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01471-z

Ten years of treatment with ruxolitinib for myelofibrosis

Ruxolitinib has been shown to not only improve splenomegaly and the burdensome symptoms associated with MF but also to improve overall survival (OS).

4.

bloodresearch.or.kr

bloodresearch.or.kr/journal/view.html?uid=2498&vmd=Full&

Real-life ruxolitinib experience in intermediate-risk ...

Overall, spleen size reduction of at least 35% (spleen response) was achieved in 56.6% and 63.3% of all cohort and INT-1 risk at any time, ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6573

Efficacy and safety of ruxolitinib in patients with lower risk ...

By week 48, 26 (65.0%) patients achieved a ≥ 50% decrease in palpable spleen length. 32 (80.0%) patients achieved a ≥ 50% reduction from ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4380721/

Efficacy, safety, and survival with ruxolitinib in patients with ...

Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥3 anemia or thrombocytopenia with longer-term ruxolitinib ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12490404/

Long-term safety and effectiveness of ruxolitinib in patients ...

At Week 144 (Day 1008), the Kaplan – Meier estimated overall survival rate was 78% in the ruxolitinib arm, 61% in the intent-to-treat control ...