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

90 Participants Needed

Trial Summary

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 and at other institutions have shown that participants with high-risk features by gene array studies tend to have shorter remissions (disappearance of signs and symptoms of myeloma) and do not survive as long as participants with low-risk myeloma. Researchers at MIRT think that one reason for this is 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.

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.

What data supports the effectiveness of the drugs used in the chemotherapy for multiple myeloma?

Research shows that thalidomide, when combined with dexamethasone, has high response rates in multiple myeloma patients, with some studies reporting up to 80% effectiveness when combined with chemotherapy. Additionally, combinations of bortezomib, cyclophosphamide, and dexamethasone have shown significant efficacy and safety for newly diagnosed multiple myeloma patients. ^{1 2 3 4 5}

Is chemotherapy for multiple myeloma generally safe for humans?

Chemotherapy drugs for multiple myeloma, like thalidomide, lenalidomide, and bortezomib, have specific side effects such as sleepiness, blood clots, and nerve damage. These side effects are usually predictable and can be managed with careful monitoring and adjusting doses, making long-term treatment possible. ^{6 7 8 9 10}

What makes this chemotherapy treatment for multiple myeloma unique?

This chemotherapy treatment for multiple myeloma is unique because it combines multiple drugs, including thalidomide, which has shown significant activity in refractory cases and can enhance response rates when combined with dexamethasone and chemotherapy. The combination of these drugs aims to improve survival rates and achieve higher response rates, especially in patients who have relapsed after transplant. ^{5 11 12 13 14}

Research Team

Frits van Rhee, MD, PhD

Principal Investigator

UAMS

Eligibility Criteria

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.

I am between 18 and 75 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

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

2. Germany 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. [2021]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. [2020]

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

Thalidomide in the management of multiple myeloma. [2019]

6. 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]

7. 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]

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

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

Addition of lenalidomide to melphalan in the treatment of newly diagnosed multiple myeloma: the National Cancer Institute of Canada Clinical Trials Group MY.11 trial. [2020]

12. 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]

13. India pubmed.ncbi.nlm.nih.gov

Comparison of Two Therapeutic Regimes, Lenalidomide with Dexamethasone and Thalidomide with Dexamethasone, in the Treatment of Multiple Myeloma at a Tertiary Care Hospital in India. [2020]

14. China pubmed.ncbi.nlm.nih.gov

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