Quadruple Therapy for Multiple Myeloma

(IMPEDE Trial)

Recruiting at 1 trial location

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: Isatuximab, Elotuzumab, Pomalidomide, Dexamethasone

Disqualifiers: Asthma, HIV, Hepatitis, Cardiac disease, 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: Ongoing 28-day cycles

53 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, open-label phase II study in subjects with relapsed and/or refractory multiple myeloma with at least two prior lines of therapy. The main study consists of three phases: a 28-day screening phase, treatment phase that consists of 28-day cycles of isatuximab with elotuzumab, pomalidomide, and dexamethasone and a follow-up phase.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug combination used in the Quadruple Therapy for Multiple Myeloma?

Research shows that combining isatuximab with pomalidomide and dexamethasone significantly improves progression-free survival (the time during which the disease does not get worse) and enhances tumor response in patients with relapsed and refractory multiple myeloma. Additionally, pomalidomide with dexamethasone alone has been effective in prolonging survival and improving response rates in similar patient groups. ^{1 2 3 4 5}

Is the quadruple therapy for multiple myeloma safe for humans?

The combination of isatuximab with pomalidomide and dexamethasone has been generally well tolerated in studies, with a manageable safety profile. Common side effects include infusion-related reactions, infections, and blood-related issues like neutropenia (low white blood cell count) and thrombocytopenia (low platelet count), but no new safety concerns have been identified. ^{1 2 5 6 7}

What makes the quadruple drug therapy for multiple myeloma unique?

The quadruple drug therapy for multiple myeloma is unique because it combines four different types of drugs: Dexamethasone (a steroid), Elotuzumab and Isatuximab (both are monoclonal antibodies that target specific proteins on cancer cells), and Pomalidomide (an immunomodulatory drug that helps the immune system fight cancer). This combination aims to improve treatment effectiveness by attacking the cancer in multiple ways, potentially leading to better outcomes compared to using fewer drugs. ^{1 2 4 5 8}

Research Team

Binod Dhakal, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults with multiple myeloma who've had at least two prior treatments, including lenalidomide and a proteasome inhibitor, can join this trial. They must have measurable disease, be in good enough health to perform daily activities (ECOG 0-2), and use effective contraception. Those allergic to similar drugs or with certain heart, lung conditions or other cancers cannot participate.

Inclusion Criteria

I agree to use effective contraception or practice abstinence during and for four months after the study.

I will use effective birth control from two weeks before until 16 weeks after my last dose of the study drug.

I am a woman who has been postmenopausal for at least a year or am surgically sterile.

Exclusion Criteria

My condition did not improve after treatment with SLAMF7 antibody.

Pregnant or breastfeeding or planning to become pregnant

You have allergies or bad reactions to monoclonal antibodies or human proteins.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Run-in Safety Phase

A safety run-in phase to assess potential dose-limiting toxicities with isatuximab, pomalidomide, elotuzumab, and dexamethasone

4 weeks

Weekly visits for drug administration and monitoring

Treatment

Participants receive isatuximab, pomalidomide, elotuzumab, and dexamethasone in 28-day cycles

Ongoing 28-day cycles

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Dexamethasone
• Elotuzumab
• Isatuximab
• Pomalidomide

Trial Overview The study tests a combination of isatuximab, pomalidomide, elotuzumab, and dexamethasone in patients whose multiple myeloma has returned after treatment. It's an open-label phase II trial where everyone gets the same drugs in repeated 28-day cycles after screening.

Participant Groups

Group I: Safety Run-in Experimental Treatment 4 Interventions

Six subjects will be enrolled. Isatuximab (10 mg/kg) intravenous (IV) on days 2, 8, 15, 22 of cycle 2 and days 1 and 15 of subsequent cycles. Pomalidomide (4 mg) by mouth (PO) days 1-21 of each cycle. Elotuzumab (10 mg/kg) on days 1, 8, 15, 22 of cycles 1 and 2; 20 mg/kg on day 1 of subsequent cycles. Dexamethasone 40 mg (20 mg if \>75 years) PO or IV on days 1, 8,15 and 22 of each cycle.

Group II: Expansion Experimental Treatment 4 Interventions

Forty-seven subjects with relapsed and/or refractory multiple myeloma will be enrolled. Isatuximab (10 mg/kg) IV on days 2, 8, 15, 22 of cycle 1 and days 1 and 15 of subsequent cycles. Pomalidomide (4 mg) PO days 1-21 of each cycle. Elotuzumab (10 mg/kg) on days 1, 8, 15, 22 of cycles 1 and 2; 20 mg/kg on day 1 of subsequent cycles. Dexamethasone 40 mg (20 mg if \>75 years) PO or IV on days 1, 8,15 and 22 of each cycle.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

Isatuximab, an anti-CD38 monoclonal antibody, significantly improves progression-free survival and tumor response when combined with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, based on phase III studies.

The combination therapies involving isatuximab were generally well tolerated, maintaining health-related quality of life and showing a manageable safety profile without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

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]

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

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]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Isatuximab, a monoclonal antibody targeting CD38, was shown to significantly improve progression-free survival in adult patients with relapsed and refractory multiple myeloma when used in combination with pomalidomide and dexamethasone, compared to pomalidomide plus dexamethasone alone.

While treatment with isatuximab was associated with a higher incidence of treatment-related adverse events, including serious complications, the overall safety profile was deemed acceptable, leading to a positive benefit-risk ratio for its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. Delgado, J., Zienowicz, M., van Hennik, PB., et al.[2021]

In a phase 2 study involving 46 patients with newly diagnosed multiple myeloma, the quadruplet regimen of elotuzumab, carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) achieved a stringent complete response (sCR) and/or measurable residual disease (MRD)-negativity rate of 58% after 8 cycles, indicating significant efficacy without the need for autologous stem cell transplant (ASCT).

The study demonstrated a 3-year progression-free survival (PFS) rate of 72% overall, and an impressive 92% for patients who achieved MRD-negativity, suggesting that MRD-guided therapy could allow for reduced treatment exposure while maintaining effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. Derman, BA., Kansagra, A., Zonder, J., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. [2022]

2. 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]

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

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

5. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]

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

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. [2021]

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

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. [2023]