Bortezomib + Lenalidomide + Dexamethasone for Multiple Myeloma

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Corticosteroids, Antivirals

Disqualifiers: Renal insufficiency, Heart failure, HIV, 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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is evaluating a combination of three drugs called lenalidomide, subcutaneous (injection under the skin) bortezomib, and dexamethasone (RVD) as a possible treatment for multiple myeloma.

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 mention that you cannot take certain corticosteroids and other specific medications. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug combination Bortezomib, Lenalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Bortezomib with Lenalidomide and Dexamethasone significantly improves progression-free survival and response rates in patients with newly diagnosed multiple myeloma, compared to Lenalidomide and Dexamethasone alone. ^{1 2 3 4 5}

Is the combination of Bortezomib, Lenalidomide, and Dexamethasone safe for treating multiple myeloma?

The combination of Bortezomib, Lenalidomide, and Dexamethasone is generally considered safe for treating multiple myeloma, with common side effects including fatigue, sensory neuropathy (nerve damage causing tingling or numbness), and blood-related issues like low white blood cell counts. Serious side effects are less common, and no treatment-related deaths were observed in studies. ^{6 7 8 9 10}

What makes the drug combination of Bortezomib, Lenalidomide, and Dexamethasone unique for treating multiple myeloma?

The combination of Bortezomib, Lenalidomide, and Dexamethasone is unique because it includes Bortezomib, a proteasome inhibitor, which when added to the standard Lenalidomide and Dexamethasone regimen, has shown to improve progression-free survival and response rates in newly diagnosed multiple myeloma patients who are not immediately undergoing stem-cell transplant. ^{1 3 4 11 12}

Research Team

Jacob Laubach, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who haven't had systemic therapy yet. They must have certain levels of monoclonal protein, organ dysfunction related to myeloma, and be able to follow the study plan. Women must test negative for pregnancy and use birth control; men should also use contraception if with a female partner of childbearing potential.

Inclusion Criteria

I have bone issues like fractures or osteoporosis, or my bone marrow has a high number of plasma cells.

A monoclonal protein (paraprotein) in either serum or urine (except in cases of non-secretory myeloma)

I've been treated with steroids for hypercalcemia or spinal cord compression but haven't exceeded the equivalent of 160 mg of dexamethasone in two weeks.

Exclusion Criteria

You are allergic to bortezomib, boron, or mannitol.

I can swallow pills.

My kidney function is low, with creatinine levels above 2.5 mg/dL or filtration rate below 45 ml/min.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive lenalidomide, subcutaneous bortezomib, and dexamethasone for 4 to 8 cycles. Stem cell mobilization occurs at the end of Cycle 4.

12-24 weeks

Multiple visits per cycle

Maintenance

High-risk participants receive subcutaneous bortezomib and lenalidomide, while standard-risk participants receive lenalidomide monotherapy.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 41.2 months

Treatment Details

Interventions

• Bortezomib
• Dexamethasone
• Lenalidomide

Trial Overview The trial tests a drug combo: lenalidomide, subcutaneous bortezomib, and dexamethasone (RVD) as initial treatment for multiple myeloma. It includes those eligible after screening based on specific health criteria like kidney function and blood cell counts.

Participant Groups

Group I: Lenalidomide, subcutaneous Bortezomib, Dexamethasone Experimental Treatment 5 Interventions

Lenalidomide (R): 25 mg on days 1-14 orally Subcutaneous Bortezomib (sqV): 1.3 mg/m\^2 on days 1, 4, 8 and 11 Dexamethasone (d): 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 Stem cell mobilization occurs at the end of Cycle 4. Participants may elect to stop treatment at the end of Induction Cycle 4 and proceed to autologous stem cell transplant (ASCT) with melphalan 200 mg/m\^2 conditioning, or receive a full 8 cycles of RsqVd induction therapy. RsqVd cycle duration is 21-days. Maintenance follows with the specific regimen determined by risk category. High-risk participants defined as those with International Staging System (ISS) stage II or stage III disease and/or high-risk cytogenetics including t(4;14), t(4; 16), del(17p) receive sqV of 1.3 mg/m\^2 on days 1 and 15 in addition to R 10mg (15mg after cycle 3 if tolerated) on days 1-21 of 28-day cycle. Standard-risk participants receive R monotherapy.

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+

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

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

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 phase 3 trial involving 402 patients with previously treated multiple myeloma, the combination of selinexor, bortezomib, and dexamethasone resulted in a median progression-free survival of 13.93 months, significantly longer than the 9.46 months observed with standard bortezomib and dexamethasone (p=0.0075).

The selinexor combination therapy was associated with lower rates of peripheral neuropathy (21%) compared to the standard treatment (34%), suggesting a safer profile regarding this common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Grosicki, S., Simonova, M., Spicka, I., et al.[2022]

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]

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]

The combination treatment of bortezomib, pulsed dexamethasone, and weekly cyclophosphamide (CVD) resulted in a high overall response rate of 75% and a complete response rate of 31% in patients with relapsed/refractory myeloma, significantly outperforming other regimens.

The safety profiles of the CVD combination were similar to those of bortezomib/dexamethasone and bortezomib alone, with comparable rates of side effects like thrombocytopenia, neutropenia, and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Davies, FE., Wu, P., Jenner, M., et al.[2022]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

In a phase III study involving 155 multiple myeloma patients, bortezomib and lenalidomide treatments showed similar effectiveness, with 15% and 18% of patients achieving a very good partial response (VGPR) respectively, indicating comparable efficacy.

Both treatment regimens resulted in similar median progression-free survival (PFS) of 16.3 months for bortezomib and 18.6 months for lenalidomide, along with comparable two-year overall survival rates of 75% and 74%, confirming their safety and effectiveness in managing multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. Montefusco, V., Corso, A., Galli, M., et al.[2020]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

References

1. 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]

2. Italy pubmed.ncbi.nlm.nih.gov

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. [2022]

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

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. [2022]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Italy pubmed.ncbi.nlm.nih.gov

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. [2020]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. [2020]

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

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]