Combination Therapy for Multiple Myeloma

Overseen By Sunita Sunita

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Maryland, Baltimore

Must not be taking: High-dose steroids

Disqualifiers: Amyloidosis, CNS disease, Plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three treatments—Belantamab Mafodotin (an antibody-drug conjugate), Cyclophosphamide (a chemotherapy drug), and Dexamethasone (a corticosteroid)—for individuals with multiple myeloma that has returned or stopped responding to other treatments. The goal is to determine the effectiveness and safety of these drugs when used together. Participants should have previously tried at least three different myeloma treatments without success and must have measurable disease markers, such as a specific protein level in their blood or urine. For those whose treatments have not worked for multiple myeloma, this trial might be suitable. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to contribute to early-stage treatment development.

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

The trial requires that you stop any systemic anti-myeloma therapy at least 14 days before starting the study treatment. Additionally, you should not have taken high-dose steroids recently. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

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

A previous study led to the FDA approval of belantamab mafodotin for treating relapsed or refractory multiple myeloma, confirming its safety in humans. However, like many treatments, it can cause side effects. Some participants reported eye problems and low blood counts.

Cyclophosphamide and dexamethasone are often used together in cancer treatments and are generally well-tolerated. Cyclophosphamide may cause nausea, hair loss, and tiredness, while dexamethasone might lead to weight gain, mood changes, and trouble sleeping.

This trial is in its early stages, so the safety of these treatments is still under close study. Early phase trials focus heavily on safety, and participation helps researchers learn more about the safety of these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Belantamab Mafodotin in combination with Cyclophosphamide and Dexamethasone for treating multiple myeloma because it offers a novel approach compared to standard treatments. Belantamab Mafodotin is an antibody-drug conjugate, which uniquely targets the BCMA (B-cell maturation antigen) on myeloma cells, delivering a potent anti-cancer agent directly to the cancer cell, minimizing damage to healthy cells. Current standard treatments often involve proteasome inhibitors and immunomodulatory drugs, which work differently and can have broader side effects. This unique targeting mechanism and the combination approach hold promise for potentially more effective and manageable treatment options for patients.

What evidence suggests that this trial's treatments could be effective for Multiple Myeloma?

Research shows that combining belantamab mafodotin, cyclophosphamide, and dexamethasone can help treat relapsed or refractory multiple myeloma. Participants in this trial will receive varying dosages of this combination in separate treatment arms. Earlier studies found that belantamab mafodotin alone helped nearly half of the patients by shrinking or eliminating their cancer. Specifically, patients experienced an average progression-free survival of 3.8 months and an overall survival of 17.2 months after starting treatment. Cyclophosphamide may enhance the function of the immune system's natural killer cells, potentially increasing the treatment's effectiveness. This combination offers hope for those who have not succeeded with other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Ashraf Badros, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma that's come back or hasn't responded to treatment. They must have tried at least three prior treatments, including specific anti-myeloma drugs, and not had certain stem cell transplants recently. Participants need good organ function, no active infections, and can't be pregnant or breastfeeding.

Inclusion Criteria

You have a certain amount of abnormal proteins in your blood or urine.

Provide signed written informed consent

I am using birth control as required by local laws for clinical study participants.

Exclusion Criteria

I am HIV positive.

I have been cancer-free from any other cancer for more than 2 years.

I have tested positive for hepatitis B recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive Belantamab Mafodotin, Cyclophosphamide, and Dexamethasone in two dose levels to assess tolerability

6 weeks

Every 3 weeks for Arm A, every 6 weeks for Arm B

Phase II Treatment

Participants receive the highest tolerated dose to assess response rate and toxicity

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Cyclophosphamide
• Dexamethasone

Trial Overview The study tests the effectiveness and safety of combining Belantamab Mafodotin with Cyclophosphamide and Dexamethasone in patients whose Multiple Myeloma has relapsed or is refractory. It aims to see how well this combination works as a treatment option.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

1. Dose level 1: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 6 weeks cycles. 2. Dose level 2: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 6 weeks cycles.

Group II: Arm A Experimental Treatment 1 Intervention

1. Dose level 1: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 3 weeks cycles. 2. Dose level 2: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 3 weeks cycles.

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 Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-belantamab-mafodotin-blmf-relapsed-or-refractory-multiple-myeloma

FDA approves belantamab mafodotin-blmf for relapsed or ... Patients were randomized (1:1) to receive either belantamab mafodotin-blmf, bortezomib, and dexamethasone (BVd) or daratumumab, bortezomib, and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04896658

Study Details | NCT04896658 | Belantamab Mafodotin ... This is a Phase I/II, open-label study to evaluate the efficacy and safety of Belantamab Mafodotin, cyclophosphamide, and dexamethasone.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1984/531919/Belantamab-Mafodotin-Plus-Cyclophosphamide-and

Belantamab Mafodotin Plus Cyclophosphamide and ... ProMMise B combines Belamaf with oral cyclophosphamide which at low doses may be synergistic through induction of T and NK cell anti myeloma ...

4. myeloma.org myeloma.org/blog/blenrep-belantamab-mafodotin-for-multiple-myeloma

Blenrep for Myeloma: Uses, Side Effects & Status Learn about Blenrep (belantamab mafodotin), a treatment for multiple myeloma. This guide covers how it works, side effects, and its current ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S295032802500038X

Belantamab mafodotin in patients with relapsed/refractory ... Belantamab mafodotin showed ORR 45%, PFS 3.8 months, and OS 17.2 months in relapsed/refractory multiple myeloma in a real-world setting.