Iberdomide + Bortezomib + Dexamethasone + Isatuximab for Multiple Myeloma

(BOREALIS Trial)

Recruiting at 1 trial location

Overseen By Amanda Garrioch

Age: 65+

Sex: Any

Trial Phase: Phase 2

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 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: 8

75 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 4 5 6}

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. ^{3 4 5 7 8}

Research Team

Martha Louzada, MD, MSc

Principal Investigator

London Health Sciences Centre

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

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

Treatment Details

Interventions

• Bortezomib
• Dexamethasone
• Iberdomide

Trial Overview 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

Who Is Running the Clinical Trial?

Canadian Myeloma Research Group

Lead Sponsor

Trials

7

Recruited

500+

Findings from Research

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 two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

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. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

In a study of 85 patients with relapsed/refractory multiple myeloma, the combination of bortezomib and dexamethasone resulted in a 55% overall response rate, with 19% achieving complete response and 35% achieving very good partial response after a median of 6 treatment cycles.

While bortezomib-dexamethasone was effective, with a median overall survival of 22 months, 78% of patients experienced peripheral neuropathy, highlighting the need for monitoring and management of this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes. Pantani, L., Zamagni, E., Zannetti, BA., et al.[2015]

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]

In a study of 16 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone resulted in a high clinical response rate of 87.5%, with 6 patients achieving near complete response.

The treatment was associated with manageable side effects, primarily gastrointestinal issues and thrombocytopenia, which were alleviated with supportive care, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. Yuan, ZG., Hou, J., Zhou, F., et al.[2015]

In a study of 23 patients with relapsed or refractory multiple myeloma, both low (1.0 mg/m2) and standard (1.3 mg/m2) doses of bortezomib combined with dexamethasone showed similar response rates, with 70% for the low dose and 61.5% for the standard dose, indicating that lower doses can be just as effective.

However, the standard dose of 1.3 mg/m2 was associated with more adverse effects, including serious infections and treatment-related deaths, suggesting that while it may be more effective, it also carries a higher risk of toxicity.

NCBI (Pubmed)

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]. Bao, L., Lu, XJ., Zhang, XH., et al.[2015]

In a phase 3 study involving 307 patients with relapsed and refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved progression-free survival (11.5 months) compared to pomalidomide and dexamethasone alone (6.5 months).

The most common side effects included infusion reactions and upper respiratory infections, with a low incidence of treatment-related deaths, indicating that isatuximab is a relatively safe and effective treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

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. Attal, M., Richardson, PG., Rajkumar, SV., et al.[2020]

In a study of 24 patients with relapsed/refractory multiple myeloma (RRMM) showing only biochemical progression, the combination of isatuximab and dexamethasone with methylprednisolone resulted in a 63% overall response rate and a 79% clinical benefit rate, indicating its efficacy.

The treatment was well tolerated, with only 5 instances of Grade ≥3 adverse events, primarily lymphocytopenia, and no severe complications related to respiratory infections, anemia, or thrombocytopenia, suggesting a favorable safety profile.

NCBI (Pubmed)

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. Regidor, BS., Jew, S., Goldwater, MS., et al.[2023]

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]

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]

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]

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]

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

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. [2015]

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]

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]

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]