Isatuximab for Smoldering Multiple Myeloma

Not currently recruiting at 2 trial locations

Overseen By Shawnee Carpenter

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Chemotherapy, CD38 drugs

Disqualifiers: Myeloma events, Pregnancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 30 cycles (28 days each)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called isatuximab, with or without lenalidomide, to determine its effectiveness for individuals with smoldering multiple myeloma, a type of blood disorder. The goal is to assess how well isatuximab slows the progression to multiple myeloma, a more severe form of the disease. Suitable candidates for this trial have smoldering multiple myeloma with specific risk factors that increase the likelihood of progression to multiple myeloma. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain treatments like corticosteroids and radiotherapy are not allowed unless they are stable chronic doses for specific conditions. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that isatuximab is likely to be safe for humans?

Research has shown that isatuximab has been tested for safety in treating multiple myeloma. In one study, infections were the most common reason for stopping treatment, affecting about 2.8% of patients. This suggests that while the drug is generally safe, infections can be a concern.

The FDA has already approved isatuximab for treating multiple myeloma, indicating some confidence in its safety based on earlier studies. However, like any treatment, it can have side effects, so monitoring for any negative reactions is important.

Overall, isatuximab appears promising, but participants should understand the potential risks and discuss them with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Isatuximab is unique because it targets a specific protein called CD38 on the surface of certain immune cells. This protein plays a key role in the survival and growth of multiple myeloma cells. Unlike traditional treatments for smoldering multiple myeloma, which often involve observation or medications like bisphosphonates, isatuximab works by triggering the immune system to attack these cancer cells directly. Researchers are excited about isatuximab because it offers a more targeted approach, potentially leading to greater effectiveness with fewer side effects compared to broader chemotherapy regimens.

What evidence suggests that isatuximab might be an effective treatment for smoldering multiple myeloma?

Research has shown that isatuximab yields promising results for treating smoldering multiple myeloma. In earlier studies, 62% of patients had no detectable cancer cells after treatment with isatuximab, marking a positive outcome. This trial will administer isatuximab alone. Although previous studies demonstrated that combining isatuximab with lenalidomide is effective and generally well-tolerated, this trial focuses solely on isatuximab. This treatment also helps slow the disease, reducing the risk of progression. Overall, these findings suggest that isatuximab could be a valuable option for managing smoldering multiple myeloma. ^{2 4 6 7 8}

Who Is on the Research Team?

Sheeba Thomas, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with high risk smoldering plasma cell myeloma, showing specific levels of monoclonal protein or bone marrow plasma cells. They must be at high risk for developing multiple myeloma and have good kidney, liver, and blood health. Women who can bear children and men with partners who can must use birth control. Exclusions include HIV, recent major surgery, uncontrolled diseases like heart failure or hypertension, prior treatments for this condition, pregnancy or breastfeeding.

Inclusion Criteria

I am at high risk of my condition progressing to multiple myeloma according to PETHEMA criteria.

I am able to get out of my bed or chair and move around.

I agree to use birth control to prevent pregnancy during the study.

Exclusion Criteria

I have not undergone radiotherapy.

I do not have any uncontrolled illnesses like high blood pressure or heart problems.

Your blood calcium levels are too high.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab intravenously with or without lenalidomide over multiple cycles

Up to 30 cycles (28 days each)

Day 1, 8, 15, 22 of cycle 1; Day 1 and 15 of cycles 2-6; Day 1 of subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Isatuximab

Trial Overview The trial is testing Isatuximab's effectiveness in patients with a pre-cancerous condition called high risk smoldering plasma cell myeloma. It's an immunotherapy that may help the immune system prevent tumor growth and spread. The study includes monitoring through lab biomarker analysis to see how well it works.

How Is the Trial Designed?

Group I: Treatment (isatuximab) Experimental Treatment 2 Interventions

Patients receive isatuximab IV over 5 hours on day 1 of cycle 1, and over 3 hours thereafter on days 8, 15, and 22 of cycle 1, on days 1 and 15 of cycles 2-6, and on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a Phase 3 trial with 302 patients suffering from relapsed/refractory multiple myeloma, the combination of isatuximab with carfilzomib-dexamethasone significantly prolonged progression-free survival (PFS) to a median of 35.7 months compared to 19.2 months for carfilzomib-dexamethasone alone.

The addition of isatuximab also resulted in higher rates of complete response (44.1% vs 28.5%) and minimal residual disease negativity (33.5% vs 15.4%), indicating improved efficacy without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Martin, T., Dimopoulos, MA., Mikhael, J., et al.[2023]

In a phase 3 study involving 302 patients with relapsed multiple myeloma, the addition of isatuximab to carfilzomib-dexamethasone significantly improved progression-free survival compared to carfilzomib-dexamethasone alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of disease progression.

While the isatuximab group experienced a higher rate of treatment-emergent adverse events (77% vs. 67%), the overall safety profile was similar, with no significant difference in fatal adverse events, suggesting that isatuximab can be safely integrated into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Moreau, P., Dimopoulos, MA., Mikhael, J., et al.[2022]

Isatuximab, a humanized IgG1 monoclonal antibody targeting CD38, was approved by the FDA in March 2020, adding a new option for treating multiple myeloma.

The use of monoclonal antibodies like isatuximab, along with other therapies such as immunomodulatory drugs and proteasome inhibitors, allows for more complex treatment regimens (3 to 4 drugs) while maintaining acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. Richter, J., Sanchez, L., Thibaud, S.[2021]

Isatuximab monotherapy was found to be well tolerated and effective in Japanese patients with relapsed/refractory multiple myeloma, with an overall response rate of 36.4% and a clinical benefit rate of 54.5%.

The study identified a recommended dose of 20 mg/kg administered weekly and bi-weekly, with a median progression-free survival of 5.6 months, indicating promising antitumor activity and an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study. Sunami, K., Fuchida, SI., Suzuki, K., et al.[2023]

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]

Isatuximab is an IgG1 monoclonal antibody that targets CD38 on cancer cells and has been approved in the USA for treating multiple myeloma in patients who have undergone at least two prior therapies.

The approval of isatuximab, in combination with pomalidomide and dexamethasone, marks a significant advancement in treatment options for adult patients with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. Dhillon, S.[2021]

Isatuximab, an anti-CD38 monoclonal antibody, was found to be well tolerated and effective in treating heavily pretreated relapsed/refractory multiple myeloma, with an overall response rate of 36.4% in a phase 2 trial involving 28 patients.

The most common side effects were mild infusion reactions occurring in 42.9% of patients, indicating a manageable safety profile, while the median progression-free survival was 4.7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. Sunami, K., Suzuki, K., Ri, M., et al.[2020]

In a Phase 1b study involving 73 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplantation, the combination of isatuximab with bortezomib-lenalidomide-dexamethasone (Isa-VRd) showed a remarkable overall response rate of 98.6%, with over half of the patients achieving a complete response.

While 79.5% of patients experienced grade ≥3 treatment-emergent adverse events, the pharmacokinetics of isatuximab remained consistent, indicating that the combination treatment does not affect its metabolism, supporting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Ocio, EM., Perrot, A., Bories, P., et al.[2023]

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]

Isatuximab, a CD38 monoclonal antibody, is effective for treating adults with relapsed/refractory multiple myeloma, particularly in combination with pomalidomide and dexamethasone after at least two prior therapies.

Nursing care for patients receiving isatuximab involves careful monitoring for adverse events like infusion reactions and neutropenia, which is crucial for providing effective patient education and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Wilmoth, J., Colson, K., Dubin, F., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12466189/

Efficacy and toxicity of treatment of smoldering multiple ... Minimal residual disease (MRD) negativity rate was 62% (95% CI, 42%–81%), and grade 3–4 adverse events (AEs) rate was 36% (95% CI, 30%–43%). As ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02960555

Study Details | NCT02960555 | Isatuximab With or Without ... This is a multi-center, open label, phase II study designed to evaluate the efficacy of isatuximab with or without lenalidomide when given to patients with high ...

3. pharmacytimes.com pharmacytimes.com/view/isatuximab-lenalidomide-demonstrates-strong-efficacy-tolerability-in-smoldering-multiple-myeloma

Isatuximab-Lenalidomide Demonstrates Strong Efficacy ... Isatuximab-Lenalidomide Demonstrates Strong Efficacy, Tolerability in Smoldering Multiple Myeloma ... These interim trial results support the ...

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

Sarclisa (isatuximab-irfc) The study included 307 patients from 96 centers across 24 countries. The main efficacy outcome measure was progression-free survival (PFS) using IMWG criteria.

5. sarclisa.com sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma At the time of this analysis, 56% (101 of 179 patients) lived progression free with SARCLISA + Kd vs 45% (55 of 123 patients) treated with Kd alone. In an ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04270409

Study Details | NCT04270409 | Isatuximab in Combination ... Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering ...

7. sarclisahcp.com sarclisahcp.com/ikema-safety-profile

IKEMA Safety - SARCLISA® (isatuximab-irfc) The most frequent adverse reactions requiring permanent discontinuation were infections (2.8%, SARCLISA + Kd; 4.9%, Kd); Dosage interruptions due to an ...

8. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/7317/490110/Isatuximab-in-Combination-with-Lenalidomide-and

Isatuximab in Combination with Lenalidomide and ... Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: updated safety run-in results.