Iberdomide Maintenance Therapy for Multiple Myeloma

Recruiting at 10 trial locations

Overseen By Heather Landau, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 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

Duration: 12 months or longer

86 Participants Needed

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?

Iberdomide has shown promising results in combination with dexamethasone for patients with multiple myeloma who have been heavily pretreated, demonstrating enhanced tumor-killing and immune-boosting effects compared to other similar drugs. ^{1 2 3 4 5}

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. ^{1 3 4 6 7}

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. ^{8 9 10 11 12}

Research Team

Gunjan Shaw, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

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.

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.

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

Trial Overview The 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

Group I: Single prior autoHCT with melphalan Experimental Treatment 1 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 autoHCT Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

The P-CAD regimen (cyclophosphamide and pirarubicin) showed a higher overall response rate of 85.7% and a median progression-free survival of 16.1 months in patients with relapse/refractory multiple myeloma, compared to the BD regimen, which had a response rate of 63.9% and a median progression-free survival of 13.7 months.

Both treatment regimens were associated with manageable adverse reactions, indicating that the P-CAD regimen is a promising and well-tolerated option for improving outcomes in patients with relapse/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of BD Regimen Combined with Cyclophosphamide and Pirarubicin in Treatment of Relapse/Refractory Multiple Myeloma]. Wang, YF., Xu, WJ., Chen, YL., et al.[2018]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lonial, S., Popat, R., Hulin, C., et al.[2022]

Multiple myeloma remains an incurable disease with increasing incidence, and while current treatments using proteasome inhibitors and immunomodulatory drugs have improved outcomes, many patients still experience relapses and resistance.

Iberdomide, a new drug with high specificity for the Ikaros and Aiolos proteins, represents a promising direction in developing more targeted therapies for multiple myeloma, potentially improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. Zhang, Z., Liu, X., Zhao, L., et al.[2022]

BCMA-directed therapies, such as antibody-drug conjugates and CAR T cells, have shown significant effectiveness in treating late-stage myeloma patients who have previously undergone various treatments, but the best order for using these therapies is still unclear.

After anti-BCMA therapy, there are several promising treatment options available, including alternative BCMA therapies and non-BCMA therapies, but more research is needed to personalize treatment strategies based on individual patient factors and disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options at the time of relapse after anti-BCMA therapy. Razzo, B., Garfall, AL., Cohen, AD.[2023]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

In a study of 198 patients with advanced-stage multiple myeloma, ibandronate did not significantly reduce the occurrence of skeletal-related events (SREs) or improve survival compared to placebo over a treatment period of 12 to 24 months.

However, patients receiving ibandronate who had a significant reduction in bone-turnover markers experienced less bone morbidity, suggesting that monitoring these markers could help identify patients who may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. Menssen, HD., Sakalová, A., Fontana, A., et al.[2018]

Recent studies suggest that thalidomide-based maintenance therapy can significantly prolong overall survival in multiple myeloma patients after autologous stem cell transplantation, marking a potential breakthrough in maintenance treatment.

Ongoing trials are investigating the effectiveness of lenalidomide and bortezomib as maintenance therapies, aiming to clarify their roles and optimize treatment strategies for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of maintenance therapy in the treatment of multiple myeloma. Badros, AZ.[2019]

Thalidomide was the first maintenance therapy to show a clear benefit in progression-free survival (PFS) for multiple myeloma patients after high-dose therapy, marking a significant advancement in treatment options.

Emerging therapies like lenalidomide and bortezomib are being investigated for their potential to reduce relapse risk, but further research is needed to determine optimal dosing, duration, and long-term effects on survival and disease aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy for myeloma: how much, how long, and at what cost? Attal, M., Roussel, M.[2020]

Multiple myeloma (MM) remains an incurable disease despite new treatments, as even the most advanced therapies cannot completely eliminate the myeloma cells, leading to eventual disease progression.

Recent studies suggest that maintenance therapy with new drugs like thalidomide, lenalidomide, and bortezomib could improve survival rates, with subcutaneous administration of bortezomib showing similar efficacy to intravenous methods but with a better safety profile, particularly regarding neurological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma]. Grosicki, S.[2015]

Continuous therapy, including the use of lenalidomide and bortezomib, has been effective in improving outcomes for both young and elderly patients with multiple myeloma due to their favorable safety profiles for long-term use.

Ixazomib, the first oral proteasome inhibitor, shows significant anti-myeloma activity both alone and in combination with other drugs, making it a promising candidate for maintenance therapy in multiple myeloma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ixazomib maintenance therapy in multiple myeloma. Offidani, M., Corvatta, L., Gentili, S., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Effect of BD Regimen Combined with Cyclophosphamide and Pirarubicin in Treatment of Relapse/Refractory Multiple Myeloma]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

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]

4. France pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. [2022]

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

Options at the time of relapse after anti-BCMA therapy. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

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]

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

Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. [2018]

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

The role of maintenance therapy in the treatment of multiple myeloma. [2019]

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

Maintenance therapy for myeloma: how much, how long, and at what cost? [2020]

11. Poland pubmed.ncbi.nlm.nih.gov

[Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Oral ixazomib maintenance therapy in multiple myeloma. [2016]