Combination Chemotherapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Arkansas

Must not be taking: Bortezomib, Boron, Mannitol

Disqualifiers: Diabetes, Heart disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

177 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination chemotherapy for multiple myeloma?

Research shows that thalidomide, when combined with dexamethasone and chemotherapy, has high response rates in multiple myeloma patients, with up to 80% responding to treatment. Additionally, Velcade combined with dexamethasone has been compared favorably to other regimens for multiple myeloma. ^{1 2 3 4 5}

What safety data exists for combination chemotherapy treatments for multiple myeloma?

Combination chemotherapy treatments for multiple myeloma, including drugs like thalidomide, dexamethasone, and cyclophosphamide, have shown various side effects. Common side effects include neuropathy (nerve damage), constipation, infections, and blood-related issues like neutropenia (low white blood cell count). Serious adverse events such as deep vein thrombosis (blood clots) and secondary cancers have also been reported, indicating the need for careful monitoring during treatment. ^{5 6 7 8 9}

What makes the combination chemotherapy for multiple myeloma unique?

This combination chemotherapy for multiple myeloma is unique because it includes a mix of drugs like Adriamycin, Cisplatin, Cyclophosphamide, Dexamethasone, Etoposide, Thalidomide, and Velcade, which work together to target the cancer in different ways. This multi-drug approach aims to enhance effectiveness by using various mechanisms of action, such as killing cancer cells directly, modulating the immune system, and preventing cancer cell division, which may offer benefits over single-drug treatments. ^{4 10 11 12 13}

What is the purpose of this trial?

With this study - Total Therapy IIIB - researchers are extending the findings of Total Therapy III based what they have learned from the first two studies (Total Therapy I and II), with new research strategies designed to explore why chromosome abnormalities found in persons with multiple myeloma affect the outcome of drug therapy used in this disease."

Research Team

Gareth Morgan, MD, PhD

Principal Investigator

UAMS Myeloma Institute for Research and Therapy

Eligibility Criteria

This trial is for patients under 75 with newly diagnosed active Multiple Myeloma needing treatment. They can have had one cycle of chemotherapy, must be able to perform daily activities (performance status 0-2), and have decent heart and lung function. Pregnant women or those with serious health issues, recent heart problems, uncontrolled diabetes, severe lung disease, or a history of other cancers are excluded.

Inclusion Criteria

I am younger than 75 years old.

My blood or urine tests show abnormal protein levels, or I have significant bone marrow cancer cells.

My lung function tests are above 50% of what's expected, or I have an exception due to my condition.

Exclusion Criteria

You are allergic to bortezomib, boron, or mannitol.

Your platelet count is less than 30 x 10^9/L, unless it is related to myeloma.

My diabetes is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction/Consolidation

Participants receive DTPACE regimen for induction and consolidation therapy

8-12 weeks

Autotransplant

Participants undergo tandem melphalan-based autotransplants

4-6 weeks

Maintenance

Participants receive Thalidomide and Dexamethasone for maintenance therapy

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

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

Trial Overview Total Therapy IIIB aims to improve outcomes in Multiple Myeloma by testing a combination of drugs: Cisplatin, Thalidomide, Dexamethasone, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide and Velcade (Bortezomib). It builds on previous Total Therapy studies to understand how chromosome abnormalities affect drug response.

Participant Groups

Group I: VDTPACE Experimental Treatment 7 Interventions

Velcade, Dexamethasone, Thalidomide, Cisplatinin, Adriamycin, Cyclophosphamide and Etoposide

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Findings from Research

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]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

In a phase II study involving 98 patients with untreated multiple myeloma, both the bortezomib-thalidomide-dexamethasone (VTD) and the cyclophosphamide-added regimen (VTDC) showed high rates of near-complete response (nCR) or better, with 51% and 44% respectively, indicating both regimens are effective induction therapies.

However, the addition of cyclophosphamide in VTDC led to increased toxicity, with higher rates of grade 3 to 4 adverse events (57% vs 47% for VTD) and no significant improvement in treatment efficacy, suggesting that VTD may be the safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. Ludwig, H., Viterbo, L., Greil, R., et al.[2022]

References

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

VAD-PECC regimen in the treatment of advanced-stage multiple myeloma. [2017]

2. Italy pubmed.ncbi.nlm.nih.gov

Melphalan-prednisone versus alternating combination VAD/MP or VND/MP as primary therapy for multiple myeloma: final analysis of a randomized clinical study. [2013]

3. China pubmed.ncbi.nlm.nih.gov

[Effect of Velcade combined with Dexamethasone on multiple myeloma]. [2015]

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

Thalidomide in the management of multiple myeloma. [2019]

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

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

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

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

7. 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]

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

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

9. France pubmed.ncbi.nlm.nih.gov

[Thalidomide with or without dexamethasone for refractory multiple myeloma]. [2013]

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

Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma. [2013]

11. 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]

12. 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]

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

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. [2022]