BLd Combination Therapy for Multiple Myeloma

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

68 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety and efficacy of the bortezomib, lenalidomide and dexamethasone combination in patients with newly diagnosed multiple myeloma. We are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

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.

What data supports the effectiveness of the drug combination therapy BLd for Multiple Myeloma?

Research shows that the combination of lenalidomide and dexamethasone is effective in treating relapsed multiple myeloma, with 52% of patients achieving partial or complete remission. Additionally, bortezomib has shown promise as a first-line treatment when combined with dexamethasone, and these drugs can be used together for greater effectiveness. ^{1 2 3 4 5}

What is the safety profile of the BLd combination therapy for multiple myeloma?

The BLd combination therapy, which includes lenalidomide, bortezomib, and dexamethasone, has been studied for safety in multiple myeloma patients. Common side effects include fatigue, muscle cramps, rash, infections, and blood-related issues like low white blood cell counts. Serious side effects are less common, and no treatment-related deaths were observed in the studies. ^{3 6 7 8 9}

What makes the BLd drug combination unique for treating multiple myeloma?

The BLd combination therapy for multiple myeloma is unique because it combines bortezomib, lenalidomide, and dexamethasone, which work together to rapidly induce remission in newly diagnosed patients, with fewer severe side effects compared to previous similar treatments. This combination is effective as a primary treatment and can lead to a high rate of complete remission when followed by intensive therapy. ^{1 3 10 11 12}

Research Team

Paul Richardson, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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 am 18 years old or older.

Exclusion Criteria

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.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. [2019]

2. England 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Adherence to and effectiveness of lenalidomide after 1 year of treatment in a real world setting. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Curative Efficacy of Lenalidomide plus Low Dose Dexamethasone for Multiple Myeloma]. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Rapid control of previously untreated multiple myeloma with bortezomib-lenalidomide-dexamethasone (BLD). [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Bendamustine, Low-dose dexamethasone, and lenalidomide (BdL) for the treatment of patients with relapsed/refractory multiple myeloma confirms very promising results in a phase I/II study. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Upfront bortezomib, lenalidomide, and dexamethasone compared to bortezomib, cyclophosphamide, and dexamethasone in multiple myeloma. [2020]