Ruxolitinib + Steroids + Lenalidomide for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+6 other locations
Overseen ByJames R Berenson, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Oncotherapeutics
Must be taking: Ruxolitinib, Steroids, Lenalidomide
Must not be taking: Strong CYP3A4 inhibitors, others
Disqualifiers: POEMS syndrome, Plasma cell leukemia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a combination of ruxolitinib, steroids, and lenalidomide in multiple myeloma patients who are not responding to current treatments. The drugs work together to block cancer growth signals, reduce inflammation, and enhance the immune response. Lenalidomide is an immunomodulatory drug developed from thalidomide, effective in multiple myeloma and approved by the FDA.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before starting. Specifically, you must not have had chemotherapy, corticosteroids, immunotherapy, or certain other treatments within a few weeks before the trial. Check with the trial team for details on your specific medications.
What data supports the effectiveness of the drug combination Ruxolitinib, Steroids, and Lenalidomide for Multiple Myeloma?
The study comparing lenalidomide plus dexamethasone to other treatments in newly diagnosed elderly myeloma patients suggests that lenalidomide, a component of the combination, is effective in treating multiple myeloma. Additionally, the use of steroids like methylprednisolone is common in multiple myeloma treatment to reduce inflammation and manage symptoms.
12345Is the combination of Ruxolitinib, Lenalidomide, and Steroids safe for treating multiple myeloma?
In a study with 49 patients, the combination of Ruxolitinib, Lenalidomide, and Steroids was generally safe, with no dose-limiting toxicities. However, some serious side effects included anemia, decreased lymphocyte count, and infections like sepsis and pneumonia.
678910How is the drug combination of Ruxolitinib, Steroids, and Lenalidomide unique for treating multiple myeloma?
This treatment is unique because it combines Ruxolitinib, a JAK inhibitor (a type of drug that blocks certain enzymes involved in inflammation), with Lenalidomide and steroids, potentially offering a novel approach by targeting different pathways in multiple myeloma compared to traditional treatments like melphalan and prednisone.
35111213Eligibility Criteria
This trial is for Multiple Myeloma patients who've had the disease progress despite previous treatments and can't have a transplant. They should be able to perform daily activities with ease (ECOG ≤ 2), not be pregnant, sign consent forms, follow the study schedule, live more than 3 months, join REVLIMID REMS™ program, take aspirin if safe, and have measurable MM with certain lab results.Inclusion Criteria
I have been treated with lenalidomide before.
I can take aspirin daily and my platelet count is above 30 x 10E9/L.
I have multiple myeloma with signs that can be measured.
+10 more
Exclusion Criteria
I am positive for HIV, hepatitis B or C, or have active or latent tuberculosis.
I have received specific treatments within certain timeframes.
I developed a peeling rash from taking thalidomide or similar medication.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Ruxolitinib, Steroids, and Lenalidomide until disease progression
54 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the combination of Ruxolitinib (Jakafi), steroids (Methylprednisolone), and Lenalidomide in those whose Multiple Myeloma has worsened. It's an early-stage trial to check how safe this mix is and how well it works against MM when other treatments haven't helped.
4Treatment groups
Experimental Treatment
Group I: Rux and Steroid until progression, then add LenExperimental Treatment3 Interventions
Subject will receive Ruxolitinib Oral Tablet \[Jakafi\] at 15mg BID, and Methylprednisolone at 40mg QOD until disease progression. Lenalidomide at 10mg QD will be added to the treatment (Ruxolitinib, Methylprednisolone) once disease progression was confirmed.
Group II: Rux Len and SteroidExperimental Treatment3 Interventions
Ruxolitinib Oral Tablet \[Jakafi\] at 5mg, 10mg or 15mg BID, Lenalidomide Oral at 5mg or 10mg QD and Methylprednisolone Oral at 40mg QOD. (Dose varies during dose escalation portion of the study)
Group III: High-dose RuxolitinibExperimental Treatment2 Interventions
Subject will receive Ruxolitinib Oral Tablet \[Jakafi\] at 20mg BID and Methylprednisolone at 40mg QOD until disease progression.
Group IV: Expanded Eligibility CriteriaExperimental Treatment3 Interventions
Subject will receive Ruxolitinib Oral Tablet \[Jakafi\] at 15mg BID, Lenalidomide at 10mg QD, and Methylprednisolone at 40mg QOD until disease progression.
Lenalidomide is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Revlimid for:
- Multiple myeloma
- Myelodysplastic syndromes
- Mantle cell lymphoma
- Follicular lymphoma
- Marginal zone lymphoma
🇺🇸 Approved in United States as Revlimid for:
- Multiple myeloma
- Myelodysplastic syndromes
- Mantle cell lymphoma
- Follicular lymphoma
- Marginal zone lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cancer Specialists, LLCJacksonville, FL
Wellness Oncology and HematologyWest Hills, CA
Global Oncology, Inc.Alhambra, CA
Comprehensive Blood and Cancer CenterBakersfield, CA
More Trial Locations
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Who Is Running the Clinical Trial?
OncotherapeuticsLead Sponsor
Incyte CorporationIndustry Sponsor
References
Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. [2020]Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).
Comparison of the efficacy and safety of tofacitinib and mavrilimumab in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. [2021]The relative efficacy and safety of tofacitinib and mavrilimumab were assessed in patients with rheumatoid arthritis (RA) presenting an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma--a retrospective population based study of 1162 patients. [2013]The combination of melphalan and prednisone (MP) has been the standard treatment of multiple myeloma (MM). Since the introduction of novel agents, the clinical outcome in MM has improved. Six randomized prospective studies with thalidomide combined with melphalan and prednisone (MPT) compared to MP have been performed, most of them showing that MPT gives a better response rate and median overall survival (OS). Amongst 1843 MM patients admitted to 15 Swedish centres, we selected all patients treated with MP and MPT in first, second, third or fourth line of therapy, in total 888 patients treated with MP and 274 with MPT. Patients were evaluated for response rate, OS and Time to Next Treatment. Multivariate Cox model analysis was made to adjust for different criteria at time for MM-diagnosis. The median OS from beginning of first line of treatment was 2.2/4.2 yrs after MP/MPT respectively, and in second, third and fourth line of treatment 1.8/2.9, 1.4/1.6 and 1.1/1.9 yrs (P
Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial. [2020]Namilumab (AMG203), an immunoglobulin G1 monoclonal antibody that binds with high affinity to granulocyte-macrophage colony-stimulating factor (GM-CSF), was evaluated in a phase II randomized, double-blind, placebo-controlled study to investigate the efficacy and safety in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR) or anti-tumour necrosis factor therapy (TNF-IR).
Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. [2018]The goal of this retrospective study was to compare the efficacy and toxicity of lenalidomide-dexamethasone (len/dex) vs. melphalan-prednisone-lenalidomide (MPR) as upfront therapy for newly diagnosed elderly patients with myeloma.
A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. [2022]Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. A phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory (RR)MM who had been treated with lenalidomide, steroids and a proteasome inhibitor and showed progressive disease at study entry. A traditional 3 + 3 dose escalation design was used to enroll subjects in four cohorts. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28 day cycle and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR) and overall response rate (ORR). Forty-nine patients were enrolled. The median age was 64 years and they had received a median of six prior treatments including lenalidomide and steroids to which 94% were refractory. No dose limiting toxicities occurred. The CBR and ORR were 49% and 36%, respectively. All responding patients were refractory to lenalidomide. Grade 3 or 4 adverse events (AEs) included anemia (17%), decreased lymphocyte count (15%), and hypophosphatemia (10%). Most common serious AEs included sepsis (9.8%) and pneumonia (7.8%). This Phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating MM. NCT03110822.
Lenalidomide: A Review in Newly Diagnosed Multiple Myeloma as Maintenance Therapy After ASCT. [2018]Lenalidomide (Revlimid®) is an immunomodulatory drug with multiple mechanisms of action against multiple myeloma. It is a thalidomide analogue, with improved potency and reduced toxicity compared with thalidomide. In the EU and USA, lenalidomide monotherapy is indicated for the maintenance treatment of patients with newly diagnosed multiple myeloma who have undergone autologous stem-cell transplantation (ASCT). In the pivotal, phase 3 IFM 2005-02 and CALGB 100104 trials, lenalidomide maintenance therapy after ASCT administered until disease progression significantly prolonged progression-free survival (PFS; primary endpoint) relative to placebo in patients with newly diagnosed multiple myeloma. These results are generally supported by those of the phase 3 GIMEMA and Myeloma XI trials. Lenalidomide maintenance therapy significantly prolonged overall survival in CALGB 100104 but not in IFM 2005-02. However, a meta-analysis of patient-level data from IFM 2005-02, CALGB 100104 and GIMEMA showed an overall survival benefit with this therapy. Lenalidomide maintenance therapy had a manageable tolerability profile in the pivotal trials. Grade 3/4 haematological adverse events and grade 3 nonhaematological adverse events were more common with lenalidomide than with placebo. Lenalidomide increased the risk of a second primary cancer, but the survival benefits outweigh this risk. In conclusion, lenalidomide maintenance therapy after ASCT until disease progression prolongs PFS and overall survival in patients with newly diagnosed multiple myeloma. Therefore, lenalidomide offers a valuable maintenance treatment option for this population.
A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. [2021]Label="PURPOSE">Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids and a proteasome inhibitor and showed progressive disease at study entry.
Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]Recent studies have shown a clinical benefit of lenalidomide, an oral immunomodulatory drug, plus dexamethasone in patients with relapsed/refractory multiple myeloma (MM). The most common grade 3-4 adverse events were cytopenias, fatigue, muscle cramps, rash, infection, insomnia, and venous thromboembolism. Lenalidomide in combination with dexamethasone has been approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of patients with MM who have received at least one prior therapy. An expert panel reviewed the efficacy and toxicity of lenalidomide plus dexamethasone, and provided recommendations on the management of patients receiving this treatment. Patient selection is straightforward, as prognostic factors do not appear to heavily influence efficacy. In addition, the panel agreed on strategies for the management of side effects. The recommendations presented here will aid the safe administration of lenalidomide, and avoid unnecessary dose reduction and discontinuation, thus assuring the best efficacy of treatment.
Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]Lenalidomide is an amino-substituted derivative of thalidomide with direct antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as antiangiogenic activity and immunomodulatory effects. Together with the introduction of bortezomib and thalidomide, lenalidomide has significantly improved the survival of patients with relapsed and refractory myeloma. The most common adverse events associated with lenalidomide include fatigue, skin rash, thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined with dexamethasone or other conventional cytotoxic agents, there is an increase in the incidence of venous thromboembolic events. There is now evidence that continued treatment with lenalidomide has a significant impact on survival by improving the depth and duration of response. This highlights the value of adverse event management and appropriate dose adjustments to prevent toxicity, and of allowing continued treatment until disease progression. In this review, we will discuss the different lenalidomide-based treatment regimens for patients with relapsed/refractory myeloma. This is accompanied by recommendations of how to manage and prevent adverse events associated with lenalidomide-based therapy.
[Treatment of patients with juvenile rheumatoid arthritis with combination of leflunomide and methotrexate]. [2018]To evaluate the efficacy and safety of the combined therapy with leflunomide and methotrexate in the patients with juvenile rheumatoid arthritis (JRA).
Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis. [2023]We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA).
Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: A retro-prospective observational study. [2023]We investigate safety and efficacy in common clinical practice of the combination of carfilzomib and dexamethasone (Kd56) approved for the ENDEAVOR trial for the treatment of relapsed or refractory multiple myeloma.