Quadruple Therapy for Multiple Myeloma

Recruiting at 2 trial locations

Overseen By Shebli Atrash, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shebli Atrash

Must not be taking: Investigational drugs, Monoclonal antibodies

Disqualifiers: Active infection, CNS involvement, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to treat multiple myeloma, a type of blood cancer. Researchers aim to determine if combining belantamab mafodotin (an antibody-drug conjugate) with standard medications can improve patient outcomes and identify any positive or negative effects. The study is open to individuals with relapsed or high-risk newly diagnosed multiple myeloma who have experienced symptoms like anemia, bone pain, or kidney problems. Participants should have tried at least one previous treatment if they have relapsed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new drug combination.

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

The trial requires a washout period of at least 14 days from any prior chemotherapy before enrollment. However, the protocol does not specify if you need to stop other current medications, so it's best to discuss this with the trial team.

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

Research has shown that combining belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone holds promise for treating multiple myeloma, though safety concerns exist. Earlier studies reported some side effects in patients, but the treatment also demonstrated positive effects against the cancer. Importantly, researchers have studied these drugs to assess their combined efficacy and minimize overlapping side effects.

Belantamab mafodotin, one of the drugs in this combination, has been tested in other studies. It showed a good response in fighting cancer, though some patients reported unwanted effects.

Overall, while this combination treatment remains under study, early results suggest it is generally well-tolerated. However, like any treatment, side effects are possible, and ongoing research is crucial to fully understand its safety. ^{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 some of the latest advancements in treatment. Unlike standard treatments like bortezomib or thalidomide, this regimen includes belantamab mafodotin, an antibody-drug conjugate that delivers a toxic payload directly to cancer cells, sparing healthy ones. This precision targeting is promising for reducing side effects and improving effectiveness. Additionally, combining belantamab mafodotin with carfilzomib, lenalidomide, and dexamethasone could enhance the overall attack on cancer cells, offering hope for more durable responses in patients.

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

Research has shown that belantamab mafodotin, when combined with drugs like carfilzomib, lenalidomide, and dexamethasone, may help treat multiple myeloma. In one study, belantamab mafodotin, a drug that targets a protein on myeloma cells, helped about 32% of patients by shrinking or eliminating their cancer. Both lab and patient studies suggest that belantamab mafodotin works well with other medications, enhancing their effects without causing many additional side effects. Previous trials have demonstrated that drug combinations with belantamab mafodotin can be more effective than other similar treatments. Overall, these findings suggest that this combination could be a strong option for patients with multiple myeloma. ^{1 2 4 5 6}

Who Is on the Research Team?

Shebli Atrash, MD, MS

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

Adults with multiple myeloma who've had at least one prior therapy can join this trial. They must have good organ function, agree to use effective contraception, and not be pregnant or breastfeeding. People with certain heart, lung, kidney conditions, active infections or other recent cancers aren't eligible. Participants need to avoid contact lenses and haven't received certain treatments recently.

Inclusion Criteria

Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative

Willing to refrain from using contact lenses while participating in this study

I have been recently diagnosed with active multiple myeloma.

Exclusion Criteria

I have not undergone plasmapheresis in the last 7 days.

I haven't had cancer in the last 5 years, except for skin cancer.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the KRd-belantamab mafodotin combination

28 days (Cycle 1)

Phase II Treatment

Efficacy and safety assessment of the combination in newly diagnosed, high-risk multiple myeloma patients

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks post treatment discontinuation

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Carfilzomib
• Dexamethasone
• Lenalidomide

Trial Overview The study is testing the effectiveness of belantamab mafodotin combined with carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma. It aims to see if this drug combo improves patient outcomes compared to current standard treatments.

How Is the Trial Designed?

Group I: Phase II Experimental Treatment 1 Intervention

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Group II: Phase I Experimental Treatment 1 Intervention

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

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?

Shebli Atrash

Lead Sponsor

Trials

3

Recruited

80+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

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

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

Published Research Related to This Trial

In a real-world study of 106 patients with relapsed or refractory multiple myeloma, belantamab mafodotin (BM) demonstrated an overall response rate of 38.1% and a median overall survival of 9.3 months, indicating its efficacy as a treatment option for heavily pre-treated patients.

The treatment was associated with significant safety concerns, particularly ophthalmic adverse events, with 48% of patients experiencing eye-related issues, including keratopathy in 37.5% of cases, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study. Talbot, A., Bobin, A., Tabone, L., et al.[2023]

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]

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]

In a study of 36 patients with multiple myeloma who had received a median of eight prior therapies, belantamab mafodotin demonstrated an overall response rate of 33%, which aligns with results from the DREAMM-2 trial.

Keratopathy was a notable side effect, affecting 43% of patients, with 8% discontinuing treatment due to this issue, highlighting the need for monitoring eye health during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience. Vaxman, I., Abeykoon, J., Dispenzieri, A., et al.[2022]

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]

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]

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]

Citations

1. 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 ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11290537/

Belantamab mafodotin, lenalidomide and dexamethasone ... Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124075098

Final Results of Phase 1 Clinical Trial of Belantamab ... In the pivotal DREAMM-2 study, belantamab mafodotin (Belamaf), an antibody-drug conjugate targeting BCMA, achieved an overall response rate (ORR) of 32% with a ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04822337

NCT04822337 | Study of Carfilzomib, Lenalidomide, ... The phase II portion of the trial is a two-stage design that will assess the efficacy and safety of the combination in newly diagnosed, high-risk MM patients.