Chemotherapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arkansas

Disqualifiers: Hypertension, Diabetes, Psychiatric illness, 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: 12-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a potentially improved method for treating multiple myeloma, a type of blood cancer that often results in shorter remission times for high-risk patients. The approach uses a combination of chemotherapy drugs in lower doses and shorter cycles. The goal is to prevent myeloma cells from regrowing between treatments, potentially leading to longer remission and improved survival. Individuals with newly diagnosed active multiple myeloma who require treatment might be suitable candidates, especially if they have experienced disease progression after being labeled with "smoldering" myeloma in the past. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants, offering an opportunity to benefit from potentially effective therapies early on.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients should not have more than one cycle of systemic multiple myeloma therapy, excluding bisphosphonates and localized radiation, before joining the trial.

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

Research has shown that the MEL-VTD-PACE treatment, a combination of several drugs, has been used to treat multiple myeloma. This regimen includes melphalan, velcade, thalidomide, dexamethasone, cisplatin, Adriamycin, cyclophosphamide, and etoposide. Studies suggest that this combination can be effective, particularly for patients with high-risk multiple myeloma.

Regarding safety, these drugs have been used in cancer treatments for some time and are generally well-tolerated. However, like most chemotherapy drugs, they can cause side effects such as tiredness, nausea, or low blood counts. In this study, the drugs are administered in lower doses and shorter cycles, which might help reduce these side effects.

Since the trial is in Phase 2, earlier studies have likely shown some safety, but researchers continue to closely monitor the treatment to ensure it is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the MEL--VTD-PACE treatment regimen for multiple myeloma because it combines several powerful drugs to target the cancer in multiple ways. Unlike standard treatments that often rely on fewer drugs, this regimen includes Melphalan, Velcade, Thalidomide, Dexamethasone, and others, offering a multi-pronged attack on the disease. Velcade, for example, works by inhibiting the proteasome, a protein complex that cancer cells need to survive, which is a different approach compared to many standard therapies. Additionally, Thalidomide modulates the immune system, potentially enhancing the body's ability to fight the cancer. This multi-agent approach could lead to more effective treatment outcomes by tackling the disease from several angles at once.

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

Research has shown that the MEL-VTD-PACE combination treatment for multiple myeloma, which participants in this trial will receive, is promising. Previous studies found that drugs like Velcade (bortezomib), thalidomide, and dexamethasone can help patients live longer and delay the disease's return. These drugs attack and kill myeloma cells, preventing them from quickly regrowing. Using lower doses in shorter treatment cycles aims to stop cancer cells from regrowing between treatments, potentially leading to longer disease-free periods. Overall, this drug combination has been linked to better outcomes compared to standard chemotherapy. ^{2 3 6 7 8}

Who Is on the Research Team?

Frits van Rhee, MD, PhD

Principal Investigator

UAMS

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with newly diagnosed active multiple myeloma that requires treatment. Participants should have high-risk disease characteristics, adequate kidney function (serum creatinine level < 3 mg/dL), and good heart and lung function. They must not have received more than one cycle of systemic therapy, excluding certain treatments like bisphosphonates.

Inclusion Criteria

I have had no or just one round of treatment for my multiple myeloma, not counting bone treatments or spot radiation.

My lung function tests are at least half of what is expected, or I have an exception due to my condition.

You need to have a certain level of heart function, as measured by a heart imaging test.

Exclusion Criteria

I haven't had cancer before, except for certain skin cancers or cervical cancer that's been treated.

My condition is not considered high-risk.

Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Subjects of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

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

12-16 weeks

Transplant

Participants undergo tandem transplants with dose-reduced MEL-80-VRD-PACE regimen

8-12 weeks

Inter-transplant Therapy

Participants receive treatment between transplants to prevent myeloma regrowth

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Maintenance Therapy

Long-term maintenance therapy to sustain remission

Long-term

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The study tests a combination of chemotherapy drugs (Cyclophosphamide, Velcade, Dexamethasone, Cisplatin, Thalidomide, Etoposide, Melphalan, Adriamycin) given in lower doses but more frequently to prevent myeloma cells from regrowing between cycles. The goal is to achieve longer remissions and improve survival time for those with high-risk myeloma.

How Is the Trial Designed?

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

Melphalan, Velcade, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide and Etoposide

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Published Research Related to This Trial

Novel therapies for multiple myeloma, such as thalidomide, lenalidomide, and bortezomib, have significantly improved patient outcomes but come with specific and manageable toxicity profiles.

Common adverse events include somnolence, venous thromboembolism, myelosuppression, gastrointestinal disturbances, and peripheral neuropathy, which can be effectively managed through patient monitoring and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of treatment-related adverse events in patients with multiple myeloma. Mateos, MV.[2018]

Thalidomide, lenalidomide, and bortezomib have significantly improved survival rates for patients with multiple myeloma, but they come with specific adverse event profiles that can impact treatment continuity.

Key adverse events include peripheral neuropathy (from thalidomide and bortezomib), venous thromboembolism (from thalidomide and lenalidomide), and myelosuppression (from lenalidomide and bortezomib), which are generally predictable and manageable with proper monitoring and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to maintain patients on long-term therapy: understanding the profile and kinetics of adverse events. Mateos, MV.[2018]

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]

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 a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9387011/

Multiple Myeloma: 2022 update on Diagnosis, Risk ... The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE).

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

Understanding Autologous Stem Cell Transplant for Myeloma The standard of care for fit multiple myeloma patients is to receive high-dose chemotherapy (HDT) with autologous stem cell rescue. This procedure is also known ...