Chemotherapy Regimen for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arkansas

Must not be taking: Thalidomide, Revlimid, Bortezomib

Disqualifiers: Severe renal dysfunction, Neurotoxicity, 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

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment outcomes for individuals with high-risk multiple myeloma, a type of blood cancer. Researchers are testing a combination of chemotherapy drugs—Adriamycin, Cisplatin, Cyclophosphamide, Dexamethasone, Etoposide, Melphalan, Thalidomide, and Velcade—administered in lower doses and shorter cycles to determine if this approach can extend remission periods. This trial is suitable for those with multiple myeloma who have undergone at least one previous round of chemotherapy or are newly diagnosed and untreated. The study targets individuals without prior transplants and seeks to prevent myeloma cells from regrowing between treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients must be able to receive full doses of the trial drugs, which might imply adjustments to your current medications. It's best to discuss this with the trial team.

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

Studies have shown that the MEL-VTD-PACE combination, which includes drugs like melphalan, Velcade (bortezomib), thalidomide, and dexamethasone, treats multiple myeloma effectively. These drugs have proven effective in other treatments and generally work well against myeloma. Research indicates that using these drugs together can control the disease better than using them separately.

Regarding safety, these drugs are usually well-tolerated but can cause side effects. Common side effects may include fatigue, nausea, and a higher risk of infection due to immune system weakening. However, healthcare teams often manage these side effects effectively.

This trial is in an intermediate phase, indicating some evidence of safety and effectiveness, but researchers are still gathering more information. Prospective participants should discuss potential risks and benefits with their doctor before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the MEL-VTD-PACE regimen for multiple myeloma because it combines several powerful drugs, including Velcade and Thalidomide, which work in unique ways to tackle cancer cells. Unlike traditional treatments that often focus on a single mechanism, this regimen targets multiple pathways, potentially increasing effectiveness and reducing the chance of resistance. Additionally, the inclusion of Velcade, a proteasome inhibitor, disrupts cancer cell functions at a molecular level, offering a novel approach compared to conventional chemotherapy options. This multi-faceted strategy gives researchers hope for improved outcomes in patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that the MEL-VTD-PACE drug combination, which participants in this trial will receive, may effectively treat multiple myeloma, a type of blood cancer. Studies have found that drugs like thalidomide and bortezomib (Velcade) can prolong the period before the cancer worsens. These drugs work well with others in the treatment plan, such as dexamethasone and melphalan, which are commonly used for multiple myeloma. The goal is to use these drugs in lower doses and shorter treatment cycles to prevent the cancer cells from returning between treatments. This approach aims to help patients remain symptom-free longer and improve their chances of survival. ^{1 2 6 7 8}

Who Is on the Research Team?

Maurizio Zangari, MD

Principal Investigator

University of Arkansas

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with symptomatic multiple myeloma, who have had prior chemotherapy or are newly diagnosed. They must have good heart and lung function, no severe past reactions to certain drugs like thalidomide or bortezomib, and no other serious illnesses that could affect the study. Pregnant women can't join, and participants must agree to use contraception.

Inclusion Criteria

Patient must have signed an IRB-approved informed consent and understand the investigational nature of the study

I have never had a bone marrow or stem cell transplant.

My heart's pumping ability is at least 40%, tested within the last 60 days or after recent chemotherapy.

Exclusion Criteria

I have POEMS Syndrome.

Platelet count < 30,000/mm3, and ANC < 1,000/μl

I have severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multi-agent chemotherapy in lower and more frequent doses to prevent myeloma cell regrowth between cycles

12 weeks

Weekly visits for chemotherapy administration

Transplant

Participants undergo a transplant phase with modified drug delivery to reduce side effects

4 weeks

Inter-therapy

Participants receive treatment between transplants to prevent myeloma regrowth

8 weeks

Maintenance

Long-term maintenance therapy to sustain remission

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Adriamycin
• Cisplatin
• Cyclophosphamide
• Dexamethasone
• Etoposide
• Melphalan
• Thalidomide
• Velcade

Trial Overview The trial tests a combination of chemotherapy drugs (Adriamycin, Etoposide, Cisplatin, Cyclophosphamide, Dexamethasone, Melphalan, Velcade & Thalidomide) in lower doses but more frequent cycles. The aim is to prevent myeloma cells from regrowing between treatments to achieve longer remission periods.

How Is the Trial Designed?

Group I: MEL-VTD-PACE Experimental Treatment 8 Interventions

Melphalan, Velcade, Thalidomide, Dexamethasone, CisPlatin, Adriamycin, Cyclophosphamide, Etoposide

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Published Research Related to This Trial

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

In patients with newly diagnosed multiple myeloma, the modified regimen of bortezomib, thalidomide, and dexamethasone (VTd-mod) using a lower thalidomide dose (100 mg/day) was found to be noninferior to the traditional higher dose (VTd-label) in terms of overall survival and progression-free survival, while showing better post-transplant response rates.

The combination of daratumumab with the VTd regimen (D-VTd) demonstrated superior efficacy compared to the traditional VTd-label, while maintaining similar safety profiles, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. Moreau, P., Hulin, C., Zweegman, S., et al.[2023]

In a pooled analysis of 1088 heavily pretreated patients with relapsed and refractory multiple myeloma, pomalidomide combined with low-dose dexamethasone demonstrated an acceptable safety profile, with the most common severe adverse events being neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%).

Adverse events were effectively managed through dose modifications and supportive care, with 24.2% of patients requiring dose reductions and 66.0% experiencing treatment interruptions, indicating that while side effects were significant, they were manageable to allow continued therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Moreau, P., Dimopoulos, MA., Richardson, PG., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7523011/

Multiple myeloma current treatment algorithms - PMC In a randomized trial, Dara-VTd was associated with improved PFS, and a trend to better OS compared to bortezomib, thalidomide, dexamethasone ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3227886/

Current Multiple Myeloma Treatment Strategies with Novel ... This review presents an overview of the most recent data using the novel agents thalidomide, bortezomib, and lenalidomide in the treatment of multiple ...

3. emedicine.medscape.com emedicine.medscape.com/article/2006866-overview

Multiple Myeloma Treatment Protocols Treatment protocols for multiple myeloma are provided below. In addition to general treatment recommendations, the following are included:

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01548573

Tandem Auto Transplantation in Myeloma Patients With < ... This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and ...

5. dailynews.ascopubs.org dailynews.ascopubs.org/do/designing-therapy-sequence-treatment-multiple-myeloma

Designing a Therapy Sequence for the Treatment of ... The well-established combination of bortezomib, lenalidomide, and dexamethasone (RVD) has shown a 43-month median progression-free survival (PFS) benefit in ...

6. myeloma.org myeloma.org/autologous-stem-cell-transplant

Understanding Autologous Stem Cell Transplant for Myeloma "Autologous" refers to the blood-making stem cells harvested from the patient to be a source of new blood cells after high-dose chemotherapy with melphalan. " ...

7. macmillan.org.uk macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/chemotherapy-for-myeloma

Chemotherapy for myeloma VTD – bortezomib (Velcade®), thalidomide and dexamethasone; VTD-PACE – VTD may sometimes be given with cisplatin, doxorubicin, cyclophosphamide and etoposide.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3904350/

Front-Line Treatment in Younger Patients With Multiple Myeloma This review discusses the current status of front-line therapy in younger patients with myeloma who are candidates for stem cell transplantation.