Ruxolitinib + Thalidomide for Myelofibrosis

Not currently recruiting at 6 trial locations

Overseen By Ellin Berman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Ruxolitinib

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining ruxolitinib and thalidomide can help treat myelofibrosis, a type of bone marrow cancer that disrupts blood cell production. The researchers aim to determine if these drugs together can shrink the cancer or cause any serious side effects. Individuals diagnosed with myelofibrosis who have been on ruxolitinib for at least three months without sufficient improvement might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like strong inducers or inhibitors of CYP3A4, and you must not have used other anti-cancer drugs or growth factors, except hydroxyurea, within 14 days before starting the study. If you are already taking Ruxolitinib, you must have been on a stable dose for at least 4 weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ruxolitinib and thalidomide has been studied for safety. In one study, patients experienced a reduction in spleen size after at least three treatment cycles, though some side effects were noted. The most common side effects included anemia (fewer red blood cells), fatigue, and a decrease in hemoglobin (the protein in red blood cells that carries oxygen).

For ruxolitinib, some patients reported serious side effects like severe thrombocytopenia (a low number of platelets in the blood, affecting clotting). Thalidomide, when studied alone or with other drugs, showed improvements in conditions like anemia and low platelet counts.

As this study is in a mid-stage phase, it suggests some understanding of the safety profile, but more research is needed to confirm how well the treatment is tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ruxolitinib and thalidomide for treating myelofibrosis because it offers a novel approach compared to standard treatments like JAK inhibitors alone. Ruxolitinib is a well-known JAK inhibitor that helps control symptoms and reduce spleen size, but adding thalidomide, which has anti-inflammatory and anti-fibrotic properties, could enhance these effects. This dual-action strategy targets not only the symptoms but also the underlying fibrosis, potentially improving outcomes for patients who may not fully benefit from existing therapies. The combination might also address issues like thrombocytopenia, a common challenge with current treatments, expanding its potential use to a wider patient group.

What evidence suggests that ruxolitinib and thalidomide could be effective for myelofibrosis?

Research has shown that using ruxolitinib and thalidomide together may help treat myelofibrosis. In this trial, participants will receive a combination of these two drugs. Ruxolitinib effectively reduces spleen size and eases symptoms for many with this condition, potentially extending patients' lives. When combined with other drugs, thalidomide has been shown to help with anemia (low red blood cell count) and thrombocytopenia (low platelet count). These findings suggest that this drug combination could help manage myelofibrosis symptoms and improve quality of life. ^{2 6 7 8 9}

Who Is on the Research Team?

Raajit K Rampal, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with myelofibrosis needing treatment, including those who've had previous treatments or are newly diagnosed with certain risk scores. Participants must be able to take oral meds, have proper organ function, and not be pregnant or breastfeeding. Men and women must use effective birth control. Those already on Ruxolitinib need a stable dose for at least 4 weeks.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

My organs are functioning well.

I am committed to following strict birth control measures and pregnancy testing if I can have children.

Exclusion Criteria

I haven't had a blood clot in my veins or lungs in the last 6 months.

I have been treated with Thalidomide and Ruxolitinib together.

I haven't taken cancer drugs other than hydroxyurea or Ruxolitinib recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ruxolitinib Run-in

Patients receive ruxolitinib treatment for 3 cycles prior to combination therapy

12 weeks

Combination Treatment

Participants receive ruxolitinib and thalidomide orally on days 1-28 of a 28-day cycle

6 cycles (24 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib
• Thalidomide

Trial Overview The study is testing the combination of two drugs: Ruxolitinib and Thalidomide, to see if they can shrink myelofibrosis cancer cells effectively. The trial will monitor both the positive outcomes and any adverse side effects from this drug combo.

How Is the Trial Designed?

Group I: Cohort B: Ruxolitinib and Thalidomide Experimental Treatment 2 Interventions

A cohort expansion, for patients with baseline thrombocytopenia, will enroll 35 additional patients After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.

Group II: Cohort A: Ruxolitinib and Thalidomide Experimental Treatment 2 Interventions

After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

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, 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 219 patients with myelofibrosis, ruxolitinib significantly improved health-related quality of life (HRQoL) and reduced disease-related symptoms over 48 weeks compared to best available therapy (BAT).

Ruxolitinib treatment led to notable enhancements in physical functioning, fatigue, and appetite, with significant improvements observed as early as week 8 and continuing throughout the study, supporting its efficacy as a treatment for symptomatic myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Harrison, CN., Mesa, RA., Kiladjian, JJ., et al.[2021]

Ruxolitinib is an effective treatment for intermediate or high-risk myelofibrosis, significantly reducing spleen size and alleviating related symptoms, which improves patients' quality of life.

While ruxolitinib can cause dose-dependent anemia and thrombocytopenia, these side effects can be managed with dose adjustments and monitoring, allowing most patients to continue treatment without permanent discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. Mesa, RA., Cortes, J.[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 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, 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 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, an oral JAK1/2 inhibitor, is effective in reducing spleen size and symptom burden in patients with intermediate and high-risk myelofibrosis, making it a valuable treatment option before hematopoietic stem cell transplantation (HSCT).

The impact of ruxolitinib on HSCT outcomes is not well understood, and there is significant variability in how it is used in patients transitioning to HSCT, highlighting the need for more research to guide treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. Ibrahim, U., Petrone, GEM., Mascarenhas, J., et al.[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]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, effectively managed dose-dependent cytopenias in patients with intermediate- or high-risk myelofibrosis through dose adjustments, as demonstrated in the COMFORT-I trial with 309 participants.

Titrated doses of ruxolitinib of 10 mg BID or higher led to significant improvements in myelofibrosis-related symptoms and reductions in spleen volume by week 24, indicating its efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Verstovsek, S., Gotlib, J., Gupta, V., et al.[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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119364031

Safety and Efficacy of Combined Ruxolitinib ... Studies of THAL in MF patients, alone and with prednisone, have demonstrated improvements in anemia and thrombocytopenia.

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/4163/425729/Safety-and-Efficacy-of-Combined-Ruxolitinib-and

Safety and Efficacy of Combined Ruxolitinib and Thalidomide ... Conclusions: The combination of THAL and RUX continues to demonstrate a promising efficacy signal in this analysis of an ongoing phase II study, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7237512/

Ruxolitinib-based combinations in the treatment of myelofibrosis Low dose thalidomide combined with prednisone had demonstrated improvements in anemia of about 50%, and the tolerance was better than that of ...

4. 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).

5. targetedonc.com targetedonc.com/view/ruxolitinib-stands-out-among-jak2-inhibitors-for-myelofibrosis

Ruxolitinib Stands Out Among JAK2 Inhibitors for ... The data from [the phase 3] COMFORT-I trial [NCT00952289] show that patients treated within 12 months of diagnosis have a better outcome in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10373260/

Ten years of treatment with ruxolitinib for myelofibrosis The most frequently reported AEs were anemia (2.8%), fatigue (2.4%), hemoglobin decreased (2.3%), platelet count decreased (2.3%), and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3228619/

Serious Adverse Events During Ruxolitinib Treatment ... Reported adverse effects of ruxolitinib therapy at the recommended dosage (25 or 10 mg twice a day) for patients with MF included grade 3/4 thrombocytopenia (39 ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1409002

Ruxolitinib versus Standard Therapy for the Treatment ... A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118620919

Clinical Safety and Efficacy of Combined Ruxolitinib ... Studies of THAL in MF patients, both alone and with prednisone, have demonstrated improvements in anemia and thrombocytopenia.