Quadruple Drug Therapy for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Larysa Sanchez
Must not be taking: NSAIDs, Aminoglycosides
Disqualifiers: Peripheral neuropathy, Kidney failure, Cardiac disease, Hepatitis, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a single center, open-label, phase 2 study in elderly (age ≥ 70) subjects with newly diagnosed multiple myeloma who are transplant ineligible. Subjects will receive subcutaneous daratumumab, dose-attenuated bortezomib, revlimid, and dexamethasone until confirmed disease progression, discontinuation of study treatment due to unacceptable drug toxicity, or other reasons. Throughout the study, subjects will be monitored closely for adverse events, laboratory abnormalities, and clinical response.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you should avoid NSAIDs, IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2 weeks of enrollment, except aspirin. It's best to discuss your current medications with the study team.
What evidence supports the effectiveness of the quadruple drug therapy for multiple myeloma?
Research shows that combinations of drugs like bortezomib, lenalidomide, and dexamethasone are effective in treating multiple myeloma, with studies indicating improved response rates and prolonged survival. Adding daratumumab to similar regimens has shown promise in achieving deeper responses, suggesting that the quadruple drug therapy could be effective.
12345What safety data exists for the combination of lenalidomide and dexamethasone in treating multiple myeloma?
Lenalidomide combined with dexamethasone is generally well tolerated in patients with multiple myeloma, though common side effects include low blood cell counts, fatigue, muscle cramps, rash, infections, trouble sleeping, and blood clots. This combination has been approved by health authorities for use in patients who have had previous treatments, and strategies are in place to manage these side effects effectively.
678910How is the quadruple drug therapy for multiple myeloma unique?
The quadruple drug therapy for multiple myeloma is unique because it combines four drugs—Bortezomib, Daratumumab, Dexamethasone, and Lenalidomide—each with different mechanisms to target the cancer more effectively. This combination aims to improve treatment outcomes by using a broader approach compared to the more common three-drug regimens.
1451112Eligibility Criteria
This trial is for people aged 70 or older with newly diagnosed multiple myeloma who can't have a stem cell transplant. They should be able to perform daily activities (ECOG ≤ 2) and have measurable disease indicators. Men must use contraception if sexually active with women of childbearing potential. People are excluded if they have certain heart, lung, kidney diseases, infections, severe allergies to the drugs being tested, or other health conditions that could affect drug absorption or pose risks.Inclusion Criteria
I am 70 or older, ineligible for a specific stem cell transplant, and can care for myself despite my myeloma.
You have a measurable amount of M-protein in your blood or urine, or abnormal results in a serum free light chain assay.
I have been newly diagnosed with multiple myeloma and have not received treatment.
+1 more
Exclusion Criteria
You have tested positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
Your platelet count is less than 75,000 cells per cubic millimeter.
I haven't had any cancer treatment in the last 3 weeks.
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Initial Treatment
Participants receive 12 cycles of daratumumab in combination with dose-attenuated VRd
48 weeks
12 visits (in-person, monthly)
Maintenance Therapy
Participants receive maintenance therapy with daratumumab and either lenalidomide or ixazomib based on cytogenetic risk status
Up to 2 years
Monthly visits (in-person)
Long-term Follow-up
Participants are monitored for safety and effectiveness after treatment
At least 1 year
Periodic visits (in-person or virtual)
Participant Groups
The study tests a combination of subcutaneous daratumumab with lower doses of bortezomib, lenalidomide (revlimid), and dexamethasone in elderly patients who cannot undergo transplantation. The treatment continues until disease progression or unacceptable side effects occur while monitoring for safety and effectiveness.
1Treatment groups
Experimental Treatment
Group I: Daratumumab with dose-attenuated VRdExperimental Treatment5 Interventions
SubQ Daratumumab with Dose-Attenuated VRd
Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
🇺🇸 Approved in United States as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
🇨🇦 Approved in Canada as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
🇯🇵 Approved in Japan as Velcade for:
- Multiple myeloma
- Mantle cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Icahn School of Medicine at Mount SinaiNew York, NY
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Who Is Running the Clinical Trial?
Larysa SanchezLead Sponsor
Ajai ChariLead Sponsor
Janssen, LPIndustry Sponsor
References
[Treatment of multiple myeloma with lenalidomide and bortezomib combination therapy]. [2018]In the past decade, the introduction of bortezomib, thalidomide, and lenalidomide has changed the treatment of multiple myeloma (MM) dramatically. Combinations of bortezomib or lenalidomide with dexamethasone have improved response rates and prolonged response duration compared with older approaches. However, many patients will relapse, and efforts to improve survival are still needed. Several clinical studies have demonstrated that bortezomib- or lenalidomide-based triplet regimens have improved activity compared with doublet regimens. Bortezomib and lenalidomide have different but overlapping mechanisms of anti-MM activity in preclinical studies. In several studies, the triplet regimens of lenalidomide, bortezomib, and dexamethasone (RVD) have shown significant efficacy and favorable tolerability in both newly diagnosed and relapsed/refractory multiple myeloma. In this review, we will focus on RVD therapy for myeloma treatment.
[New drugs for myeloma]. [2019]Thalidomide, administered orally, bortezomib (Velcade) intravenously and lenalidomide (Revlimid), also orally, are three agents that act on myeloma relapse. Thalidomide acts by a variety of mechanisms and is toxic to the peripheral nervous system as well as teratogenic. It acts in synergy with dexamethasone. Recent results prove that its use as first-line treatment combined with oral conventional "MP" chemotherapy improves survival in patients older than 65 years. Its use as first-line treatment with this chemotherapy appears likely. Bortezomib is the first drug in the proteasome inhibitor class. It too is toxic to the peripheral nervous system and synergistic with dexamethasone. Several studies show its efficacy as first-line 'induction treatment' with dexamethasone, in patients to receive a subsequent autologous stem cell transplantation. The combination of bortezomib and "MP" is also promising. Lenalidomide, a structural analog of thalidomide, is effective in relapsing patients. Its toxicity is essentially hematologic. It is also synergistic with dexamethasone and promising as first-line treatment. These different drugs can be used successively at relapse, making myeloma a chronic disease. They can also be used together for greater effectiveness. These combinations will replace conventional chemotherapies in the future.
Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. [2018]The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.
Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. [2022]The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple myeloma (MM). The Intergroupe Francophone du Myélome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM.
Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study. [2023]The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone; VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone; D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd.
Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program. [2018]The efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) in Chinese patients with relapsed/refractory multiple myeloma (RRMM) was demonstrated in a phase 2, multicenter trial (MM-021). MM-024 was an Extended Access Program (EAP) that allowed responding patients in the MM-021 trial to continue to receive Rd, and to provide additional safety and efficacy data with longer follow-up.
Dose-adjusted Lenalidomide Combined with Low-dose Dexamethasone Rescues Older Patients with Bortezomib-resistant Multiple Myeloma. [2018]The aim of this study was to assess the safety and efficacy of lenalidomide (Len), with the dose adjusted according to the renal function, plus low-dose dexamethasone (Dex) in older patients with bortezomib (Bor)-resistant multiple myeloma (MM).
A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]Lenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting.
Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. [2020]Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy. The FDA approved lenalidomide with a restricted distribution program, RevAssist.
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.
Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. [2021]Bortezomib (Velcade) is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in multiple myeloma (MM). In the present protocol, bortezomib was combined with other active substances like bendamustine and prednisone (BPV), in order to assess the efficacy and toxicity of the combination therapy in patients with relapsed or refractory MM.
Bortezomib in multiple myeloma: a practice guideline. [2015]Bortezomib (Velcade™, PS-341), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma. We created a provincial guideline for the use of bortezomib, in newly diagnosed individuals (both eligible and ineligible for transplant) and in individuals with relapsed or refractory multiple myeloma.