Combination Therapy for Multiple Myeloma

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Pomalidomide, Dexamethasone

Must not be taking: Systemic steroids

Disqualifiers: Waldenström's, Amyloidosis, POEMS, 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: 6-24 months

83 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs to help people with multiple myeloma that has worsened and stopped responding to standard treatments. The drugs under study are belantamab mafodotin (an antibody-drug conjugate), carfilzomib, pomalidomide, and dexamethasone. Participants fall into two groups: those who have previously received CAR T-cell therapy and those who have not. Individuals who have tried at least two other treatments without success and find their daily life significantly affected by multiple myeloma might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from new therapies.

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 must not have used an investigational drug or approved systemic anti-myeloma therapy within 14 days before starting the study treatment.

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

Research has shown that the combination of belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone raises some safety concerns, but it also holds promise for treating multiple myeloma. In previous trials with patients whose myeloma had returned or was not responding to treatment, some side effects occurred. However, the treatment demonstrated benefits, suggesting effectiveness.

Belantamab mafodotin, in particular, has undergone extensive study. One large study compared it with bortezomib and found better results when used with pomalidomide and dexamethasone. This suggests it can work well, even if some side effects occur.

The treatment is currently in a phase 2 trial, indicating it has already been tested on people to some extent. This phase focuses on understanding its effectiveness and closely monitoring its safety. While some risk of side effects exists, reaching this stage means it has shown enough promise and safety in earlier tests to justify further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for multiple myeloma because it brings together four powerful drugs: belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone. Unlike traditional treatments that often focus on just one mechanism, this regimen uses belantamab mafodotin, an antibody-drug conjugate, to target and deliver toxins directly to cancer cells. This approach is complemented by carfilzomib, a proteasome inhibitor, and pomalidomide, an immunomodulatory agent, which work together to enhance the immune system's ability to fight cancer. This multi-faceted strategy could potentially offer a more effective attack on multiple myeloma compared to standard care options, which typically involve single or dual drug therapies.

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

This trial will evaluate the effectiveness of a combination of four drugs—belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone—in treating multiple myeloma. Research has shown that this combination may benefit patients whose myeloma has returned or did not respond to other treatments. One study demonstrated that this combination worked well for such patients. Another study found that using belantamab with pomalidomide and dexamethasone was more effective than using bortezomib. Many patients treated with these combinations experienced tumor shrinkage or halted cancer growth. Although safety concerns exist, these findings suggest this treatment could be promising for those with hard-to-treat multiple myeloma. Participants in this trial will be divided into two cohorts based on their prior CAR T-Cell Therapy status to further assess the treatment's effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Benjamin Derman, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults with relapsed multiple myeloma who've had at least two prior treatments can join this trial. They should be in decent health, understand the study, and agree to use contraception. Those with certain allergies, infections, bleeding disorders or unstable heart conditions cannot participate.

Inclusion Criteria

I am willing to follow the safety rules for my cancer treatment.

My insurance covers pomalidomide and dexamethasone.

My organ functions are within the normal range as required.

Exclusion Criteria

I haven't had radiotherapy to multiple sites within the last 3 weeks.

I have a mild eye surface condition, not severe corneal disease.

I do not have Hepatitis B, or if I do, it meets specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone for 6-24 months

6-24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Carfilzomib
• Dexamethasone
• Pomalidomide

Trial Overview Researchers are testing a combination of belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone on patients whose multiple myeloma has worsened after standard treatment including CAR T-cell therapy.

How Is the Trial Designed?

Group I: Cohort 2: Prior CAR T-Cell Therapy Experimental Treatment 4 Interventions

This cohort will consist of 64 participants who have had prior CAR T-Cell Therapy. Participants will receive belantamab mafodotin, carfilzomib, pomalidomide and dexamethasone.

Group II: Cohort 1: No Prior CAR T-Cell Therapy Experimental Treatment 4 Interventions

This cohort will consist of 19 participants who have not had CAR T-Cell Therapy. Participants will receive belantamab mafodotin, carfilzomib, pomalidomide and dexamethasone.

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

Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

The combination of pemetrexed and cisplatin has been shown to induce high response rates in malignant pleural mesothelioma (MPM), a type of lung cancer that has been resistant to chemotherapy.

The review highlights a key phase III clinical trial that led to the FDA approval of pemetrexed, indicating its significant role in the treatment of MPM, with ongoing research expected to further clarify its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma. Goudar, RK.[2022]

Belantamab mafodotin (BLENREP) received accelerated FDA approval for treating relapsed or refractory multiple myeloma in adults who have undergone at least four prior therapies, showing an overall response rate of 31% to 34% in the DREAMM-2 trial with 2.5 or 3.4 mg/kg doses.

The most common side effect was keratopathy, affecting 71% to 77% of patients, leading to a boxed warning for ocular toxicity, indicating the need for careful monitoring and a restricted distribution program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Baines, AC., Ershler, R., Kanapuru, B., et al.[2023]

Pemetrexed disodium is a multitargeted antifolate that works by inhibiting key enzymes involved in DNA synthesis, making it effective against various solid tumors, including breast cancer.

When combined with gemcitabine, pemetrexed disodium shows promising clinical activity for treating metastatic breast cancer, indicating its potential as a combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Pemetrexed disodium in treating breast cancer. Adjei, AA.[2022]

Belantamab mafodotin (belamaf) is an effective treatment for relapsed or refractory multiple myeloma, showing a 32% overall response rate in the phase II DREAMM-2 study with 95 patients.

While most patients experienced microcyst-like epithelial changes (MECs) as a side effect, these were generally manageable, with a high resolution rate and no permanent vision loss reported, indicating a need for careful monitoring and collaboration between eye care and oncology professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq, AV., Degli Esposti, S., Popat, R., et al.[2020]

In the DREAMM-2 study, after 13 months of follow-up, 32% of patients with relapsed or refractory multiple myeloma achieved an overall response to belantamab mafodotin (belamaf) at a dose of 2.5 mg/kg, indicating its efficacy in a heavily pretreated population.

The study found that belamaf maintained clinical activity without new safety concerns, even in patients experiencing prolonged dose delays due to corneal events, suggesting it is a safe treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Lonial, S., Lee, HC., Badros, A., et al.[2022]

The combination of pemetrexed and carboplatin as first-line chemotherapy for malignant pleural mesothelioma showed a moderate overall response rate of 25% among 76 patients, with 21% achieving partial responses and 4% complete responses.

While the treatment was associated with some toxicity, with 47.3% of patients experiencing grade 3 hematological toxicity, the overall safety profile was considered acceptable, and the median survival for patients was estimated at 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Castagneto, B., Botta, M., Aitini, E., et al.[2020]

In a phase II clinical study involving 102 patients with malignant pleural mesothelioma, the combination of pemetrexed and carboplatin resulted in an objective response rate of 18.6%, with 65.7% of patients achieving disease control.

The treatment was well tolerated, with mild toxicity reported; grade 3 or 4 neutropenia occurred in 9.7% of cycles, and the median overall survival was 12.7 months, suggesting that this combination could be a viable alternative to the standard treatment with pemetrexed and cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. Ceresoli, GL., Zucali, PA., Favaretto, AG., et al.[2022]

Pemetrexed, a new antimetabolite, has shown promising results in treating malignant pleural mesothelioma (MPM), achieving response rates of up to 45%.

When combined with cisplatin, pemetrexed increases median survival for MPM patients to over 12 months, establishing this combination as the standard first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard therapy for the treatment of malignant pleural mesothelioma. Vogelzang, NJ.[2019]

Belantamab mafodotin (belamaf) significantly improves overall survival (OS) and duration of response (DoR) in patients with relapsed/refractory multiple myeloma compared to selinexor plus low-dose dexamethasone, with a hazard ratio of 0.53 for OS and 0.41 for DoR, indicating its efficacy as a treatment option.

Belamaf also shows a favorable safety profile, with fewer severe adverse events compared to selinexor plus dexamethasone, making it a promising single-agent therapy for patients who have already undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. Prawitz, T., Popat, R., Suvannasankha, A., et al.[2022]

In a study of 156 patients with relapsed and refractory multiple myeloma, belantamab-mafodotin (belamaf) demonstrated an overall response rate of 41.8%, with significant improvements in progression-free survival for those achieving at least minimal response (MR).

The safety profile of belamaf was manageable, with corneal events being the most common adverse effects, affecting 87.9% of patients, though only 1.3% discontinued treatment due to ocular toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. de la Rubia, J., Alonso, R., Clavero, ME., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2403407

Belantamab Mafodotin, Pomalidomide, and ... Data from a phase 1–2 trial involving patients with relapsed or refractory myeloma showed some safety concerns but promising clinical activity of belantamab ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05789303

NCT05789303 | Study of Belantamab Mafodotin With ... The purpose of this research is to gather information on the safety and effectiveness of belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone for ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4751/533572/Final-Results-of-Phase-1-Clinical-Trial-of

Final Results of Phase 1 Clinical Trial of Belantamab ... Moreover, in the DREAMM-8 trial, Belamaf outperformed bortezomib in combination with pomalidomide and dexamethasone. We, therefore, aimed to ...

4. nature.com nature.com/articles/s41408-024-01135-2

a subgroup analysis of the ALGONQUIN trial In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA105

Results from the randomized phase 3 DREAMM-8 study of ... Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus ...