Quadruple Therapy for Multiple Myeloma

(VICD Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Binod Dhakal, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Medical College of Wisconsin

Disqualifiers: Other malignancies, CNS involvement, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a single-arm, open-label phase II study with a safety lead-in phase.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that no prior multiple myeloma-directed therapy is allowed except for specific medications like dexamethasone, bortezomib, and cyclophosphamide under certain conditions. It's best to discuss your current medications with the study team to get a clear answer.

What data supports the effectiveness of the drug combination Bortezomib, Velcade, Cyclophosphamide, Cytoxan, Neosar, Endoxan, Dexamethasone, Decadron, Dexone, Hexadrol, Isatuximab, Sarclisa, isatuximab-irfc, SAR-650984 for treating multiple myeloma?

Research shows that isatuximab, when combined with other drugs like dexamethasone, improves progression-free survival (the time during which the disease does not get worse) in multiple myeloma patients. Additionally, a similar four-drug regimen including bortezomib, cyclophosphamide, and dexamethasone has shown high response rates in patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is the quadruple therapy for multiple myeloma safe for humans?

The quadruple therapy, which includes drugs like isatuximab, bortezomib, cyclophosphamide, and dexamethasone, has been generally well tolerated in studies for multiple myeloma, showing a manageable safety profile with common side effects like fatigue, infections, and blood cell count changes. Serious side effects were less common, and the treatment was considered safe enough for further studies. ^{1 2 5 6 7}

What makes the quadruple drug therapy for multiple myeloma unique?

The quadruple drug therapy for multiple myeloma is unique because it combines four different drugs, including isatuximab, which is a monoclonal antibody that targets a specific protein on cancer cells, with bortezomib, cyclophosphamide, and dexamethasone. This combination aims to enhance treatment effectiveness by using multiple mechanisms to attack the cancer, potentially improving outcomes compared to traditional three-drug regimens. ^{1 2 4 8 9}

Research Team

Binod Dhakal, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for adults with multiple myeloma who haven't had much prior treatment, can perform daily activities (ECOG 0-2), and have measurable disease. They must be able to give consent, agree to use contraception if necessary, and be eligible for stem cell transplantation. Exclusions include other cancers, central nervous system involvement by myeloma, significant heart issues or other conditions that could affect the study.

Inclusion Criteria

I am 18 years old or older.

I am eligible for a high-dose therapy and stem cell transplant according to my hospital's rules.

I am a man and will use effective contraception or practice abstinence.

Exclusion Criteria

I haven't had major surgery within the last two weeks and don't plan any during the study.

I do not have any serious heart conditions.

You have HIV, hepatitis B, or untreated hepatitis C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial cohort of patients receive treatment to assess safety

4 weeks

4 visits (in-person)

Treatment

Participants receive Bortezomib, Isatuximab, Cyclophosphamide, and Dexamethasone

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 weeks

Treatment Details

Interventions

• Bortezomib (Proteasome Inhibitor)
• Cyclophosphamide (Alkylating Agent)
• Dexamethasone (Corticosteroid)
• Isatuximab (Monoclonal Antibodies)

Trial Overview The trial tests a combination of drugs: Bortezomib, Isatuximab, Cyclophosphamide and Dexamethasone in patients eligible for stem cell transplant. It's an open-label phase II study which means everyone gets the same treatment and both doctors and patients know what's being given.

Participant Groups

Group I: Safety Lead-in Cohort A Experimental Treatment 4 Interventions

Six transplant-eligible multiple myeloma patients with renal impairment will be enrolled. Bortezomib (1.5 mg/m\^2) subcutaneous on days 1,8 and 15 Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22 Cyclophosphamide (250 mg/m\^2) IV on days 1, 8 and 15 Dexamethasone 20 mg PO or IV (10 mg if \>75 years) on days 1, 2, 8, 9,15,16, 22 and 23

Group II: Expansion Cohort A Experimental Treatment 4 Interventions

35 transplant-eligible multiple myeloma patients with renal impairment will be enrolled. Bortezomib (1.5 mg/m\^2)subcutaneous on days 1, 8 and 15 Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22 Cyclophosphamide (250 mg/m\^2) IV on days 1, 8 and 15 Dexamethasone 20 mg PO or IV (10 mg if \>75 years) on days 1, 2, 8, 9,15,16, 22 and 23

Bortezomib is already approved in Canada, Japan for the following indications:

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Kansas Medical Center Kansas City, KS

Froedtert Hospital & the Medical College of Wisconsin Milwaukee, WI

Rush University Medical Center Chicago, IL

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Patients Recruited

1,180,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. Regidor, BS., Jew, S., Goldwater, MS., et al.[2023]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are 4-Drug Regimens Here to Stay? Role in Induction and Salvage Therapies. Richter, J., Jagannath, S.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. Kim, YK., Sohn, SK., Lee, JH., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Mikhael, J., Richardson, P., Usmani, SZ., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Ocio, EM., Perrot, A., Bories, P., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. Harrison, SJ., Perrot, A., Alegre, A., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. Derman, BA., Kansagra, A., Zonder, J., et al.[2023]

References

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

Isatuximab: A Review of Its Use in Multiple Myeloma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. [2023]

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

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]

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

Are 4-Drug Regimens Here to Stay? Role in Induction and Salvage Therapies. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. [2022]

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

A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. [2021]

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

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. [2021]

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

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. [2023]