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

160 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the chemotherapy regimen for multiple myeloma?

Research shows that thalidomide, when used with dexamethasone and chemotherapy, has high response rates in multiple myeloma patients, with some studies reporting up to 80% effectiveness. Additionally, a combination of cyclophosphamide, dexamethasone, and thalidomide (CDT) showed a 90% response rate in relapsed or refractory multiple myeloma patients. ^{1 2 3 4 5}

What safety data exists for chemotherapy regimens used in multiple myeloma treatment?

The safety data for chemotherapy regimens in multiple myeloma shows that combinations like bortezomib, dexamethasone, cyclophosphamide, and lenalidomide are generally well tolerated, though some patients experienced serious side effects like febrile neutropenia (fever with low white blood cell count) and herpes zoster. Thalidomide and dexamethasone can cause side effects such as sedation, constipation, and increased risk of blood clots. Pomalidomide with dexamethasone is associated with adverse events like pneumonia and sepsis, but careful management can help patients continue treatment. ^{6 7 8 9 10}

What makes this chemotherapy regimen for multiple myeloma unique?

This chemotherapy regimen is unique because it combines multiple drugs, including Adriamycin, Cisplatin, Cyclophosphamide, Dexamethasone, Etoposide, Melphalan, Thalidomide, and Velcade, which are used in various combinations to target multiple myeloma from different angles. The inclusion of drugs like Thalidomide and Velcade, which have shown effectiveness in relapsed or refractory cases, offers a comprehensive approach that may improve response rates and manage the disease more effectively compared to standard treatments. ^{3 7 9 11 12}

What is the purpose of this trial?

There have been four previous Total Therapy (TT1 through IIIB) studies for multiple myeloma at the MIRT from 1989 to present. Results have shown that participants treated on these studies had better outcomes (meaning they have lived longer and had better responses to treatment) when compared to individuals treated with standard chemotherapy. Past studies conducted at the MIRT have shown that participants presenting to MIRT who have already received treatment for myeloma tend to have shorter remissions (disappearance of signs and symptoms of myeloma) and do not survive as long as participants who come to MIRT with untreated myeloma. Researchers at MIRT think that one reason for this is may be that the myeloma cells re-grow in the time when participants are not receiving treatment because they are recovering from high-dose chemotherapy. In this study, participants will receive several chemotherapy drugs previously shown to be effective in myeloma, but in lower doses and in shorter cycles. It is hoped that by giving the drugs in this way, myeloma cells will not have time to re-grow between cycles, therefore resulting in longer remissions. This study is being done in an attempt to improve the remission rate and the survival time for participants with high-risk myeloma.

Research Team

Maurizio Zangari, MD

Principal Investigator

University of Arkansas

Eligibility Criteria

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

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

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

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

Exclusion Criteria

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

I have POEMS Syndrome.

I have severe heart failure.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical observation of DECP combination chemotherapy for relapsing and refractory multiple myeloma patients with extramedullary plasmacytomas]. [2014]

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

Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease. [2019]

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

Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. [2013]

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

Thalidomide in the management of multiple myeloma. [2019]

5. Australia pubmed.ncbi.nlm.nih.gov

Therapeutic experience of vincristine/cyclophosphamide/melphalan or mitoxantrone/prednisone combination therapy plus thalidomide as first-line induction therapy for newly diagnosed multiple myeloma in a single institution of China. [2018]

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

Chemoresistant myeloma: phase II clinical study with low-dose thalidomide plus high-dose dexamethasone. [2019]

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

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. [2019]

8. England 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. [2018]

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

Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. [2021]

10. Switzerland 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. [2022]

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

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. [2017]

12. United States 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. [2023]