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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of four drugs to treat multiple myeloma, a type of blood cancer. Researchers aim to determine if this combination benefits patients whose cancer has returned or hasn't responded to at least two previous treatments. Participants will engage in different phases, including taking medication in 28-day cycles. This trial suits those who have previously tried treatments involving lenalidomide and a proteasome inhibitor, but their cancer remains active. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that isatuximab increased the risk of serious infections and low white blood cell counts, known as neutropenia. Only a few patients discontinued treatment due to infections. Pomalidomide often causes tiredness, low blood cell counts, and sometimes blood clots. Elotuzumab has been linked to blood-related issues in many patients, but it is usually used with other treatments for multiple myeloma. Dexamethasone can increase the likelihood of infections, but reducing the dose did not affect the treatment's effectiveness. Researchers have studied these treatments for safety in other settings, and they are generally well-tolerated, though serious side effects can occur. Close monitoring of participants during the trial is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this quadruple therapy for multiple myeloma because it combines four powerful drugs—Dexamethasone, Elotuzumab, Isatuximab, and Pomalidomide—to potentially enhance treatment effectiveness. Unlike standard treatments, which often involve just one or two medications, this regimen targets multiple pathways involved in myeloma growth and survival. Isatuximab and Elotuzumab are monoclonal antibodies that specifically target proteins on myeloma cells, possibly leading to stronger immune responses. By integrating these drugs, the hope is to improve outcomes for patients with relapsed or refractory multiple myeloma who have limited options.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will evaluate a combination of isatuximab, pomalidomide, dexamethasone, and elotuzumab for multiple myeloma. Studies have shown that combining isatuximab, pomalidomide, and dexamethasone helps patients with multiple myeloma live longer without disease progression. Isatuximab directly targets cancer cells and aids the immune system in fighting them. Research suggests that adding elotuzumab to pomalidomide and dexamethasone enhances treatment effectiveness. This combination has significantly improved outcomes for patients whose multiple myeloma has returned or not responded to previous treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Binod Dhakal, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04835129

Study Details | NCT04835129 | Isatuximab, Pomalidomide, ... The study hypothesis is that the isatuximab in combination with elotuzumab, pomalidomide, and dexamethasone (Isa-EPD) will be safe and lead to superior response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215383/

Isatuximab-pomalidomide-dexamethasone versus ... Identifier: NCT02990338) demonstrated improved progression-free survival (PFS) and a benefit in overall survival (OS) was reported with the ...

3. haematologica.org haematologica.org/article/view/11970/78174

Comparison of isatuximab-pomalidomide-dexamethasone Advances in multiple myeloma (MM) treatment have sig- nificantly improved survival, yet most patients ultimately relapse and develop refractory disease.

4. myeloma.org myeloma.org/sarclisa-isatuximab-irfc

Sarclisa (isatuximab-irfc) Sarclisa is a targeted anti-myeloma therapy that binds to and kills myeloma cells directly. It also recruits surrounding immune cells to enhance its myeloma- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9870233/

Elotuzumab Plus Pomalidomide and Dexamethasone for ... In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved ...

6. myeloma.org myeloma.org/dexamethasone

Dexamethasone Data from both studies showed that dexamethasone dose reductions did not have a negative impact on outcomes in patients with newly diagnosed multiple myeloma ( ...

7. ashpublications.org ashpublications.org/blood/article/145/1/3/534803/Down-with-dex

Down with dex! | Blood | American Society of Hematology In conclusion, dexamethasone-sparing strategies can reduce steroid-induced toxicity and allow for patients to continue long-term myeloma ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4694963/

Dexamethasone-induced cell death is restricted to specific ... We demonstrated that the pro-death effect of dexamethasone is related to the genetic heterogeneity of MM because sensitive cell lines were restricted to MAF ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/dexamethasone-oral-route/description/drg-20075207

Dexamethasone (oral route) - Side effects & dosage This medicine may cause you to get more infections than usual. Avoid people who are sick or have infections and wash your hands often. If you ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265020303323

Comparative Safety, Bioavailability, and Pharmacokinetics ... This study compared the safety, rate, and extent of absorption of a single dose of an orally administered 20-mg dexamethasone tablet to five 4-mg tablets ( ...