Iberdomide + Bortezomib + Dexamethasone + Isatuximab for Multiple Myeloma

(BOREALIS Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Martha Louzada, MD, MSc

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Canadian Myeloma Research Group

Must not be taking: Steroids, Immunosuppressants, CYP3A4/5 drugs

Disqualifiers: Unstable cardiac disease, Renal failure, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will evaluate efficacy and tolerability of iberdomide, bortezomib, dexamethasone and isatuximab on demand administered in combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require strong inhibitors or inducers of CYP3A4/5, which are certain types of drugs that affect how your body processes medications.

What data supports the effectiveness of the drug combination Iberdomide, Bortezomib, and Dexamethasone for treating multiple myeloma?

Research shows that Iberdomide, when combined with dexamethasone, has strong cancer-fighting and immune-boosting effects in multiple myeloma models. Additionally, Bortezomib and Dexamethasone together have been effective in treating relapsed or hard-to-treat multiple myeloma, with many patients experiencing significant improvement.

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Is the combination of Iberdomide, Bortezomib, and Dexamethasone safe for humans?

Research shows that Bortezomib and Dexamethasone, when used together, have been studied for safety in treating multiple myeloma, with some reports suggesting that adjusting the dose of Bortezomib can reduce stomach-related side effects. Iberdomide, when combined with Dexamethasone, has also been evaluated for safety in patients with multiple myeloma, showing potential for safe use in heavily pretreated patients.

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What makes the drug combination of Iberdomide, Bortezomib, Dexamethasone, and Isatuximab unique for treating multiple myeloma?

This drug combination is unique because Iberdomide is a novel agent that enhances the immune system and works well with other drugs like dexamethasone, bortezomib, and isatuximab, which target multiple pathways in multiple myeloma. This combination aims to improve treatment outcomes by leveraging the synergistic effects of these drugs.

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Eligibility Criteria

This trial is for individuals aged 65 or older with newly diagnosed multiple myeloma, who haven't been treated yet. They must have certain levels of monoclonal proteins in their blood or urine and signs of organ damage related to the disease. Participants need to understand the study and agree to follow its schedule.

Inclusion Criteria

I am 65 years old or older.

My myeloma is causing organ problems.

i. [C] Calcium elevation in the blood (serum calcium >2.75 mmol/L or >0.25 mmol/L higher than the upper limit of normal) ii. [R] Renal insufficiency (serum creatinine >177 µmol/L) iii. [A] Anemia (hemoglobin <100 g/l or 2 g < laboratory normal) iv. [B] Lytic bone lesions or osteoporosis

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive Iberdomide, Bortezomib, and Dexamethasone for upfront treatment. Isatuximab is added for those not achieving VGPR or MRD negativity after 4 cycles.

16 weeks

4 cycles (each cycle is 28 days)

Intensification

Continued treatment with Iberdomide, Bortezomib, and Dexamethasone for cycles 5-8.

16 weeks

4 cycles (each cycle is 28 days)

Maintenance

Ongoing treatment with Iberdomide, Bortezomib, and Dexamethasone from cycle 9 onwards.

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests a combination treatment using Iberdomide, Bortezomib, Dexamethasone, and Isatuximab added as needed. It aims to see how effective this regimen is for treating multiple myeloma and how well patients tolerate it.

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 Nearby Select from list below to view details:

Princess Margaret Hospital Toronto, Canada

London Health Sciences Centre London, Canada

Who Is Running the Clinical Trial?

Canadian Myeloma Research Group Lead Sponsor

References

1. 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] 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.

2. Italy pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. [2022] The efficacy and safety of added dexamethasone were assessed in patients with relapsed and/or refractory multiple myeloma who had a suboptimal response to bortezomib alone.

3. Germany pubmed.ncbi.nlm.nih.gov

Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes. [2015] Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse.

4. 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] 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.

5. China pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. [2015] To investigate the efficacy and toxicity of bortezomib in combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma(MM).

6. China pubmed.ncbi.nlm.nih.gov

[Effects of bortezomib at different doses in combination with dexamethasone in treatment of relapsed or refractory multiple myeloma: a comparative study]. [2015] To investigate the efficacy and toxicity of bortezomib of different doses in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma (MM).

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

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. [2020] Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.

8. England pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. [2023] Isatuximab is approved for treatment of relapsed/refractory multiple myeloma (RRMM) with dexamethasone and carfilzomib or pomalidomide. Patients receiving these three-drug regimens have exhibited more Grade ≥ 3 adverse events (AEs) compared to the two-drug class combination of isatuximab and steroids alone. Thus, this single-center retrospective study investigated the efficacy of isatuximab with dexamethasone and methylprednisolone (ISAdm) for RRMM patients showing only biochemical progression (BP) of their disease.