Ruxolitinib for Lymphoma

Recruiting at 9 trial locations

Overseen By Steven M. Horwitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Antivirals

Must not be taking: Ruxolitinib

Disqualifiers: Uncontrolled illness, Ruxolitinib, 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: Unknown

Duration: Variable (until disease progression or study termination)

82 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that any previous systemic anti-cancer therapy for T-cell lymphoma must be stopped at least 2 weeks before starting the study drug. However, glucocorticoids (a type of steroid) can be used to control symptoms if reduced to 20mg or less, and topical steroids for skin conditions are allowed.

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

Ruxolitinib, a drug that blocks certain proteins involved in cell growth, has shown some activity in treating relapsed or hard-to-treat Hodgkin lymphoma, with a small percentage of patients experiencing partial responses. While its effects were short-lived, it was generally well-tolerated, suggesting it might be useful when combined with other treatments. ^{1 2 3 4 5}

Is Ruxolitinib generally safe for humans?

Ruxolitinib has been studied for safety in various conditions, showing some side effects like skin reactions and anemia (low red blood cell count), but it is generally considered safe for use in humans. In animal studies, it did not increase cancer risk, and in a study with Japanese patients, most completed treatment without serious issues. ^{6 7 8 9 10}

How is the drug Ruxolitinib unique for treating lymphoma?

Ruxolitinib is unique because it is an oral drug that inhibits Janus kinases (JAK) 1 and 2, which are involved in the signaling pathways that can contribute to cancer growth. This mechanism of action is different from many traditional chemotherapy treatments, which often target rapidly dividing cells more broadly. ^{2 7 11 12 13}

What is the purpose of this trial?

The purpose of this study is to test any good and bad effects of the study drug called ruxolitinib. Ruxolitinib works by blocking a protein called JAK. JAK works along with another protein called STAT and is important for survival of many T or NK-cell lymphomas. By blocking JAK, ruxolitinib may cause T or NK-cell lymphomas to shrink.

Research Team

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with relapsed or refractory T or NK cell lymphoma who've had at least one prior systemic therapy can join this trial. They must have measurable disease, adequate blood counts, and organ function. Those with HIV may participate if treated and without active infections. Pregnant women, individuals in poor health, or those on certain other treatments are excluded.

Inclusion Criteria

Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or; ≤ 3 x ULN if documented hepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's ; AST and ALT ≤ 3 x ULN; ≤ 5 x ULN if due to lymphoma involvement

I have HIV but am on treatment and have no active infections.

Measurable disease defined by:

Exclusion Criteria

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

I have been treated with ruxolitinib before.

I need help with my daily activities due to my health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib 20mg BID orally on 28-day cycles. Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

Variable (until disease progression or study termination)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Ruxolitinib

Trial Overview The trial is testing Ruxolitinib's effectiveness for shrinking T or NK-cell lymphomas by blocking a protein called JAK that helps these cancer cells survive. Participants will receive Ruxolitinib to see how well it works against their lymphoma.

Participant Groups

Group I: with rel/ref PTCL with functional evidence of JAK/STAT Experimental Treatment 1 Intervention

Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours). Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

Group II: with rel/ref PTCL who do not meet criteria for cohort 1 or 2. Experimental Treatment 1 Intervention

Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours).Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

Group III: rel/ref PTCLtumors are known to contain mutations associ Experimental Treatment 1 Intervention

Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours). Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

Group IV: Rare sub-type expansion cohort: T-PLL and T-LGL & any T-Cell/NK Lymphoma with JAK fusion mutations. Experimental Treatment 1 Intervention

Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

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+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Thomas Jefferson University

Collaborator

Trials

475

Recruited

189,000+

Findings from Research

Ruxolitinib, the first JAK2 inhibitor, has significantly improved symptoms, spleen size, and overall survival in patients with myelofibrosis compared to traditional chemotherapy, but about 50% of patients discontinue it after 3 years due to resistance or intolerance.

While second-generation tyrosine kinase inhibitors have been tested for patients who discontinue ruxolitinib, they have not shown significant effects on disease progression, highlighting the need for new treatments that target different pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitors. Breccia, M., Assanto, GM., Laganà, A., et al.[2023]

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]

In a 3-year follow-up of the COMFORT-II Trial involving 219 patients with myelofibrosis, ruxolitinib demonstrated sustained reductions in spleen size and improved quality of life, with 45% of patients remaining on treatment after 3 years.

Ruxolitinib was well tolerated, with manageable side effects like anemia and thrombocytopenia, and it was associated with longer overall survival compared to the best available therapy, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Cervantes, F., Vannucchi, AM., Kiladjian, JJ., et al.[2022]

In a phase II study involving 33 patients with relapsed/refractory Hodgkin lymphoma, ruxolitinib, a JAK1/2 inhibitor, demonstrated a modest overall response rate of 9.4% after six cycles, with a best overall response rate of 18.8%, indicating some therapeutic activity despite the advanced stage of the disease.

Ruxolitinib was generally well-tolerated, with 42.4% of patients experiencing adverse events, primarily anemia, but no severe cases of neutropenia or thrombocytopenia, suggesting it may be safely combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. Van Den Neste, E., André, M., Gastinne, T., 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]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

Ruxolitinib, a treatment for myelofibrosis, has been associated with a case of EBV reactivation leading to a severe lymphoproliferative disorder in a 57-year-old female patient, highlighting a potential risk of opportunistic infections.

This case emphasizes the need for close monitoring of patients on Ruxolitinib for signs of viral reactivations and opportunistic infections, as they may pose serious health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. Pálmason, R., Lindén, O., Richter, J.[2022]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

Ruxolitinib, a JAK1 and JAK2 inhibitor used for myelofibrosis and polycythemia vera, showed no carcinogenic potential in long-term studies with Tg.rasH2 mice and Sprague-Dawley rats, indicating it does not increase cancer risk.

Despite some pharmacological effects like lymphoid depletion and inflammation, ruxolitinib did not affect survival rates or increase neoplastic findings, suggesting it is safe for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. Shuey, DL., Oliver, J., Zhou, G., et al.[2021]

Ruxolitinib is shown to be safe and effective for treating myelofibrosis in Japanese patients, with 86.3% of the 51 participants completing the 24-week study and no deaths reported.

At 24 weeks, 30% of patients had significant reductions in spleen size, and there were notable improvements in symptoms and quality of life, even among those with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. Komatsu, N., Kirito, K., Shimoda, K., 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]

Ruxolitinib is an effective oral treatment for myelofibrosis, showing significant and lasting improvements in symptoms and splenomegaly in patients from major clinical trials, including the phase III COMFORT-I and -II studies with a survival advantage for those treated with ruxolitinib.

While ruxolitinib can cause dose-related anemia and thrombocytopenia, these side effects are manageable and rarely lead to treatment discontinuation, highlighting the importance of monitoring and dosage adjustments for optimal patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a review of its use in patients with myelofibrosis. Plosker, GL.[2021]

Ruxolitinib, a JAK1/2 inhibitor recently approved for Myelofibrosis, significantly reduces nitric oxide production and pro-inflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in RAW 264.7 cells, indicating its potential anti-inflammatory effects.

In an endotoxemia model with C57 mice, ruxolitinib improved survival rates by 70% and decreased serum levels of pro-inflammatory cytokines, suggesting it may be a promising therapeutic candidate for sepsis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice. Li, L., He, X., Wang, X., et al.[2022]

References

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

Novel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitors. [2023]

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

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

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

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. [2021]

5. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]

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

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. [2021]

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

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. [2022]

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

Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. [2021]

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

Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a review of its use in patients with myelofibrosis. [2021]

13. China pubmed.ncbi.nlm.nih.gov

Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice. [2022]