BLd Combination Therapy for Multiple Myeloma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Corticosteroids, Antivirals

Disqualifiers: Peripheral neuropathy, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a combination of three drugs—bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Decadron, Dexone, or Hexadrol)—for individuals with newly diagnosed multiple myeloma, a type of blood cancer. Researchers seek to identify the highest dose combination that can be administered safely. This trial may suit those diagnosed with multiple myeloma who have not yet received treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of bortezomib, lenalidomide, and dexamethasone, often called RVd, is generally safe and well-tolerated by patients. Studies have found that this treatment has a good safety record, with most patients experiencing positive results and few serious side effects.

One study indicated that this combination is usually safe for most people, allowing them to undergo the treatment without major issues. However, like any treatment, some side effects can occur, such as tiredness, low blood cell counts, or stomach problems. Proper care can manage most of these side effects.

In summary, the combination of bortezomib, lenalidomide, and dexamethasone has been tested and found safe for many people. It is important to discuss any concerns and possible side effects with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for multiple myeloma, which often involve separate administration of drugs, the BLd combination therapy integrates bortezomib, lenalidomide, and dexamethasone into a single regimen. This combination targets the cancer cells through different mechanisms: bortezomib inhibits proteasomes, lenalidomide modulates the immune system, and dexamethasone reduces inflammation. Researchers are excited because this approach could potentially enhance treatment effectiveness by attacking the disease on multiple fronts simultaneously. Additionally, the structured schedule, which includes a rest period, may help manage side effects and improve patient quality of life during treatment.

What evidence suggests that the BLd combination therapy could be effective for multiple myeloma?

In this trial, participants will receive a combination of the drugs bortezomib, lenalidomide, and dexamethasone. Earlier studies have shown that this combination is highly effective for treating newly diagnosed multiple myeloma. Research indicates that this treatment is not only effective but also generally well-tolerated by patients. Specifically, data from these studies suggest that patients experienced significant improvements in their condition. This combination therapy is considered a strong option for those newly diagnosed with multiple myeloma, offering promising results in managing the disease. ^{3 4 6 7 8}

Who Is on the Research Team?

Paul Richardson, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed multiple myeloma who haven't had systemic therapy before. They should be relatively active (Karnofsky score ≥60) and not pregnant. Exclusions include serious illnesses, prior cancers (with some exceptions), renal insufficiency, low blood counts, liver enzyme abnormalities, certain heart conditions, uncontrolled diabetes or infections, known drug allergies and HIV.

Inclusion Criteria

I have not received any systemic therapy for my multiple myeloma.

You have to have a negative pregnancy test from a blood or urine sample.

I have been diagnosed with multiple myeloma.

Exclusion Criteria

Serious medical or psychiatric illness likely to interfere with participation in study

You have signs of bleeding from your mouth or inside your body, or your platelets are not working properly.

I do not have any serious infections or health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bortezomib, lenalidomide, and dexamethasone combination therapy in 21-day cycles for up to 8 cycles

24 weeks

Weekly visits for drug administration and monitoring

Maintenance

Participants with stable or responding disease may continue treatment on a maintenance schedule

As per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Dexamethasone
• Lenalidomide

Trial Overview The study tests the safety and effectiveness of a combination therapy using Bortezomib, Lenalidomide, and Dexamethasone in patients with new multiple myeloma. It aims to find the highest safe dose of this mix and how well it works together as an initial treatment.

How Is the Trial Designed?

Group I: lenalidomide, dexamethasone, bortezomib combination Experimental Treatment 3 Interventions

In this study each cycle will be 21 days and participants will begin the study medication in the clinic on Cycle 1 Day 1. Lenalidomide (capsules) will be taken daily for the first 2 weeks only (Day 1-14). Dexamethasone (tablets) will be taken on Day 1, 2, 4, 5, 8, 9, 11 and 12. Bortezomib will be given intravenously in the outpatient treatment clinic on Day 1, 4, 8 and 11. The third week is a rest period and no study medication will be given.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Published Research Related to This Trial

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

Thalidomide, when used as a first-line treatment combined with conventional chemotherapy, has been shown to improve survival rates in patients over 65, despite its potential toxicity to the peripheral nervous system.

Bortezomib and lenalidomide, both effective in treating myeloma relapse, can be used in combination with dexamethasone and each other, indicating a shift towards using these agents to manage myeloma as a chronic disease rather than relying solely on traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. Moreau, P.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3324254/

Lenalidomide, bortezomib, and dexamethasone ... Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma.

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/647/503047/Comparison-of-Response-and-Survival-Outcomes-in

Comparison of Response and Survival Outcomes in Standard ... Introduction: The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is highly effective for newly diagnosed myeloma (NDMM) ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01440582

Combination Therapy of Lenalidomide/Bortezomib ... Bortezomib, lenalidomide, and dexamethasone with panobinostat for front-line treatment of patients with multiple myeloma who are eligible for ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39486091/

Comparison of Time to Next Treatment or Death ... - PubMed Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6349658/

The Safety Profile of Concurrent Therapy for Multiple ... Our study found that that patients can safely receive palliative radiation therapy while on biological agents.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10460706/

Efficacy and safety analysis of bortezomib-based triplet ... During the follow-up period, the best outcome assessments achieved were 53.8% complete response (CR) and 84.6% excellent partial response (VGPR) ...

8. haematologica.org haematologica.org/article/view/haematol.2022.282624

Clinical perspectives on the optimal use of lenalidomide ... The combination of lenalidomide, bortezomib, and dexamethasone (RVd) has consistently demonstrated a tolerable safety profile with significant ...