Iberdomide Maintenance Therapy for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must be taking: Lenalidomide
Must not be taking: Chronic immunosuppressants
Disqualifiers: Prior allogeneic transplant, CNS involvement, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
The purpose of this study is to see if iberdomide is a safe and effective maintenance therapy option for people with Multiple Myeloma (MM) who have had an Autologous Hematopoietic Stem Cell Transplant (AHCT) and have already had lenalidomide as maintenance therapy. Patients will receive iberdomide treatment beyond 12 months if they continue to derive benefit from the treatment and will continue until progression of disease or unacceptable toxicity. Follow-up will be as per standard of care for a patient on maintenance therapy, and patients will not require additional research samples.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, ongoing treatment with chronic immunosuppressants is not allowed, and you must be willing to take DVT prophylaxis while on iberdomide maintenance.
What data supports the effectiveness of the drug Iberdomide for multiple myeloma?
Is Iberdomide safe for humans?
Iberdomide has been studied in combination with dexamethasone for patients with multiple myeloma, focusing on its safety and clinical activity. While specific safety data for Iberdomide alone is not detailed, it is part of a class of drugs known as immunomodulatory drugs, which have shown serious side effects in some cases, such as pneumonia and sepsis. Further research is needed to fully understand its safety profile.13467
How is the drug Iberdomide unique in treating multiple myeloma?
Iberdomide is a novel drug for multiple myeloma maintenance therapy, potentially offering a new mechanism of action compared to existing treatments like thalidomide, lenalidomide, and bortezomib, which are already being explored for their roles in maintenance therapy. While the specific details of Iberdomide's uniqueness are not provided, it represents an ongoing effort to find more effective maintenance therapies with acceptable toxicity profiles.89101112
Eligibility Criteria
This trial is for adults aged 18-75 with Multiple Myeloma who've had a stem cell transplant and lenalidomide maintenance therapy. They must have adequate organ function, no severe recent bleeding or other cancers, not be pregnant, agree to contraception if of childbearing potential, and have no serious infections or immune conditions.Inclusion Criteria
My hemoglobin level is above 8 g/dL without recent blood transfusions.
I had a specific bone marrow transplant for myeloma and am on a maintenance treatment.
My kidney function, measured by creatinine clearance, is adequate.
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Exclusion Criteria
I have not had serious bleeding in the last 30 days.
My multiple myeloma has spread to my brain or spinal cord.
I have had an organ transplant and am on drugs to suppress my immune system.
See 13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive iberdomide as maintenance therapy for Multiple Myeloma after AHCT
12 months or longer
Follow-up
Participants are monitored for safety and effectiveness after treatment as per standard of care
Treatment Details
Interventions
- Iberdomide (Immunomodulatory Agent)
Trial OverviewThe study tests whether Iberdomide is safe and effective as a long-term maintenance treatment for Multiple Myeloma patients post-stem cell transplant. Participants will continue treatment until disease progression or unacceptable side effects occur.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Single prior autoHCT with melphalanExperimental Treatment1 Intervention
Participants have not experienced disease progression since initiation of initial systemic anti-myeloma therapy, are within 12 months of frontline autoHCT with
\>/=140mg/m2 of melphalan, initiated lenalidomide maintenance at least 6 months ago, and have a very good partial response (VGPR) or less at time of enrollment. Cohort 1 will be initiated after evaluation of preliminary efficacy and safety data from Cohort 2.
Group II: 2 to 3 prior lines of systemic anti-myeloma therapy +/- prior autoHCTExperimental Treatment1 Intervention
Participants have already received lenalidomide maintenance after a prior line of treatment, underwent a salvage autoHCT within the prior 2-6 months as consolidation therapy for relapsed disease after 2 to 3 prior therapies
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
Medical College of Wisconsin (Data Collection Only)Milwaukee, WI
Memoral Sloan Kettering Basking Ridge (Consent and Followup)Basking Ridge, NJ
Weill Cornell Medical College (Data Collection Only)New York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
From the bench to the bedside: emerging new treatments in multiple myeloma. [2023]Within the last decade, several novel classes of anti-myeloma therapeutics have become available. The clinical successes achieved by thalidomide, lenalidomide, and the proteasome inhibitor bortezomib, and in particular the ability of these agents to lead to major clinical responses in patients resistant to conventional or high-dose chemotherapy, have highlighted the importance of expanding further the spectrum of classes of agents utilized for the treatment of myeloma. Herein, we review the current status for the development of novel anti-myeloma agents, with emphasis on classes of therapeutics which have already translated into clinical trials or those in advanced stages of preclinical development. These include second-generation proteasome inhibitors (NPI-0052 and PR-171), heat shock protein 90 (hsp90) inhibitors, 2-methoxyestradiol, histone deacetylase (HDAC) inhibitors (e.g. SAHA and LBH589), fibroblast growth factor receptor 3 (FGF-R3) inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, mTOR inhibitors, monoclonal antibodies, and agents specifically targeting the tumor microenvironment, such as defibrotide.
[Effect of BD Regimen Combined with Cyclophosphamide and Pirarubicin in Treatment of Relapse/Refractory Multiple Myeloma]. [2018]To compare the efficacy and safety of BD regimen combined with cyclophosphamide(CTX) and pirarubicin chemotherapy(P-CAD) for patients with relapse/refractory multiple myeloma(MM).
Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]Iberdomide is a novel cereblon E3 ligase modulator with enhanced tumouricidal and immune-stimulatory effects compared with immunomodulatory drugs. In preclinical myeloma models, iberdomide has shown synergy with dexamethasone, proteasome inhibitors, and CD38 monoclonal antibodies. We aimed to evaluate the safety and clinical activity of iberdomide plus dexamethasone in patients with heavily pretreated relapsed or refractory multiple myeloma.
A review on the treatment of multiple myeloma with small molecular agents in the past five years. [2022]Multiple myeloma is currently incurable, and the incidence rate is increasing year by year worldwide. Although in recent years the combined treatment plan based on proteasome inhibitors and immunomodulatory drugs has greatly improved the treatment effect of multiple myeloma, most patients still relapse and become resistant to current treatments. To solve this problem, scientists are committed to developing drugs with higher specificity, such as iberdomide, which is highly specific to ikaros and aiolos. This review aims to focus on the small molecular agents that are being researched/clinically used for the treatment of multiple myeloma, including the target mechanism, structure-activity relationship and application prospects of small molecular agents.
Options at the time of relapse after anti-BCMA therapy. [2023]B-cell maturation antigen (BCMA)-directed therapies, including antibody-drug conjugates, bispecific antibodies (BsAbs), and chimeric antigen receptor T cells (CARTs), have shown remarkable efficacy in patients with late-line myeloma with prior exposure to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. However, optimal sequencing of these agents remains to be determined, and management of these patients once they relapse has become a new unmet need. Fortunately, there are multiple options with demonstrated activity after anti-BCMA therapy, including a different BCMA-directed therapy, non-BCMA-directed CARTs and BsAbs, novel non-T-cell-engaging drugs, and standard triplet/quadruplet regimens or salvage stem cell transplant. Factors to consider when choosing a next therapy after anti-BCMA therapy include patient characteristics and preferences, prior therapies and toxicities, disease biology, timing from last anti-BCMA therapy, and, in the future, BCMA expression and immune profiling. While current data are limited to retrospective studies and small prospective cohorts, the serial use of T-cell-engaging therapies looks particularly promising, especially as BCMA-directed therapies move up earlier in the myeloma treatment course and additional CARTs and BsAbs against alternative targets (eg, G protein-coupled receptor, family C, group 5, member D and Fc receptor-homolog 5) become available. Going forward, ongoing prospective studies, large real-world data sets, and better tools to interrogate antigen expression and immune cell fitness hopefully will provide further insight into how to best individualize therapy for this difficult-to-treat population.
Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]Objective: In recent years, the emergence of immunomodulatory drugs (IMiDs) has significantly improved clinical outcomes in patients with multiple myeloma (MM); however, serious adverse events (AEs) have hindered their safe clinical application. This study aimed to characterize the safety profiles and differences in IMiDs through a disproportionality analysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing surveillance database. Methods: This study filtered reports of thalidomide, lenalidomide, and pomalidomide as primary suspect drugs in FAERS files from January 2013 to December 2021. AEs in the reports were retrieved according to the preferred terms (PTs) of the Medical Dictionary for Regulatory Activities. Furthermore, we detected safety signals using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian belief propagation neural network (BCPNN). When all three algorithms showed an association between the target drug and the AE, a positive signal was generated. Results: We extracted 9,968 thalidomide, 231,926 lenalidomide, and 55,066 pomalidomide AE reports. AEs were more common in male patients and in those >44 years old. Important safety signals were detected based on the system organ classes (SOC), including thalidomide (cardiac disorders: ROR, 2.87; PRR, 2.79; IC 1.22), lenalidomide (gastrointestinal disorders: ROR, 2.38; PRR, 2.27; IC 0.75), and pomalidomide (respiratory, thoracic, and mediastinal disorders: ROR, 2.14; PRR, 2.09; IC 0.85). Within the PT level, we identified novel risk signals: the thalidomide-induced second primary malignancy (SPM) signal was significant; lenalidomide reduced the success rate of hematopoietic stem cell collection; and three IMiDs may cause human chorionic gonadotropin increase, but this needs to be proven by clinical data. Pneumonia, sepsis, and renal failure are common risk factors for death due to IMiDs. Compared with thalidomide and lenalidomide, pomalidomide has a lower risk of venous thromboembolism (VTE) and is beneficial to patients with renal insufficiency. Conclusion: Mining data from FAERS resulted in novel AE signals, including adenocarcinoma of colon, harvest failure of blood stem cells, and increased levels of human chorionic gonadotropin. Further investigation is required to verify the significance of these signals. Moreover, IMiDs showed differences in safety reports, which should be emphasized by clinicians.
Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. [2015]To establish the clinical use of bortezomib with fewer adverse events, we retrospectively analyzed the efficacy and safety of bortezomib plus dexamethasone (BD) therapy for relapsed or refractory multiple myeloma.
Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. [2018]Bisphosphonates have been found to reduce the incidence of skeletal-related events (SREs) in patients with multiple myeloma. This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients.
The role of maintenance therapy in the treatment of multiple myeloma. [2019]Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades, without evidence of clear benefit until recently. Chemotherapy maintenance offers no benefit after conventional or high-dose treatment. Interferon-based maintenance is associated with minimal improvements in clinical outcomes, but is poorly tolerated. Results of corticosteroid maintenance studies have been conflicting; at least one randomized trial showed improved survival with prednisone maintenance after conventional chemotherapy. The role of the novel agents thalidomide, lenalidomide, and bortezomib as maintenance is emerging. Most reported maintenance studies have evaluated thalidomide, alone or in combination with a corticosteroid. Several of these studies suggest that thalidomide-based maintenance prolongs overall survival after autologous stem cell transplantation. Important questions that have not yet been resolved include the optimal dose and duration of thalidomide, whether clinical benefit depends on response to induction therapy and risk for relapse, and whether reported benefits are caused by cytoreduction or eradication of minimal residual disease, especially with bortezomib maintenance. Ongoing randomized trials are evaluating lenalidomide and bortezomib maintenance therapies to better define the role of these drugs as maintenance in multiple myeloma.
Maintenance therapy for myeloma: how much, how long, and at what cost? [2020]Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades and has been without evidence of clear advantage in terms of progression-free survival (PFS) until the mid-2000s. Neither conventional chemotherapy, prednisone, nor interferon-based maintenance regimens offered any benefit after conventional or high-dose therapy. Thalidomide was the first drug, mainly given as maintenance after high dose therapy, to demonstrate clinical benefits in terms of PFS and, in some studies, of overall survival (OS). The role of other novel agents such as lenalidomide and bortezomib as maintenance therapy is emerging. Lenalidomide has been shown to reduce the risk of relapse with longer follow-up needed to see if this will translate into a survival benefit. At present, a number of key questions remain unanswered. What are the optimal dose and duration of those treatments? Is the risk of toxicity and second primary malignancies acceptable? Will the disease be more aggressive at time of relapse? Is the clinical benefit predicted by initial prognostic factors and response to previous therapy? Does maintenance therapy work by further eradication of minimal residual disease or by immunological control of the malignant clone? Ongoing randomized trials are evaluating lenalidomide and bortezomib, both in the transplant and nontransplant settings, to better define the role of these drugs as maintenance in multiple myeloma.
[Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma]. [2015]Multiple myeloma (MM) despite the introduction to clinical practice of a new drugs in the last years, and still searching of new points of the handle for targeting treatment, remaining incurable disease. Even most intensive and most modern induction-consolidation regimens is not in the state to eradicate of the clone of myeloma, and even complete remission in immunofixation the most often after some time ends progression. Optimal way of maintenance treatment is still searching, which would be maximally effective near acceptable toxicity. Now hypothesis about possible successful maintenance therapy, which may prolong survival of MM patients became more actual in the face of the introduction to the studies with maintenance of a new drugs as: thalidomide, lenalidomide and bortesomib. The expectations on the essential progress to establish the optimal bortesomib-based regimen of the maintenance treatment in MM cause the results of the studies with its subcutaneous administration, which proved comparable efficacy with advantage in toxicity profile, especially neurological in comparison to classic intravenous way.
Oral ixazomib maintenance therapy in multiple myeloma. [2016]Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib.