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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of chemotherapy drugs to better understand and treat multiple myeloma, a type of blood cancer affecting plasma cells in the bone marrow. The drugs under study include Adriamycin, Cisplatin (Platinol), Cyclophosphamide (Cytoxan), Dexamethasone, Etoposide (Eposin), Thalidomide (Thalomid), and Velcade. Researchers aim to determine how chromosome abnormalities in patients might impact the effectiveness of these drugs. Participants newly diagnosed with active multiple myeloma requiring treatment, who have not received more than one cycle of chemotherapy, may be eligible to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that the combination treatment VDTPACE, which includes Velcade, Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, and Etoposide, has been tested in previous studies for multiple myeloma. These studies indicate that while patients experience side effects, the treatment remains manageable when doses are adjusted as needed. For example, Thalidomide may start at a lower dose and increase if the patient tolerates it well. This approach helps reduce the treatment's impact on patients.

Although side effects occur, no serious unexpected safety issues have been consistently reported. This treatment is part of ongoing research aimed at improving outcomes for multiple myeloma patients, especially by considering different genetic factors that might influence patient responses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the VDTPACE treatment for multiple myeloma because it combines several powerful drugs to potentially enhance effectiveness. Unlike standard treatments that typically use fewer agents, VDTPACE integrates Velcade and Thalidomide with a mix of chemotherapy drugs like Adriamycin and Cyclophosphamide. This combination targets the cancer cells in multiple ways, potentially increasing the chance of reducing the disease more quickly and effectively. Additionally, the inclusion of Velcade, a proteasome inhibitor, offers a unique mechanism by blocking the cancer cells' ability to break down proteins, which can lead to their death. This multifaceted approach gives researchers hope for improved outcomes in fighting this challenging cancer.

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

Research shows that the VDTPACE treatment, which participants in this trial will receive, includes the drugs Velcade, Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, and Etoposide. It effectively treats patients with multiple myeloma, particularly those whose disease has returned after previous treatments. Studies have demonstrated that this combination can serve as a successful backup treatment when others have failed. Specifically, one study found that patients who received VDTPACE had a significant response, meaning the treatment helped reduce or control their cancer. Additionally, the treatment is generally tolerable, allowing patients to manage the side effects reasonably well. This makes it a promising option for those facing difficult cases of multiple myeloma. ^{1 2 3 5 6}

Who Is on the Research Team?

Gareth Morgan, MD, PhD

Principal Investigator

UAMS Myeloma Institute for Research and Therapy

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35466165/

Bortezomib-thalidomide-dexamethasone-cisplatin- ... VTD-PACE is an effective and tolerable salvage regimen and feasible bridging therapy for SCT. Keywords: VTD-PACE; bridging therapy; relapsed or refractory ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT116010

Clinical outcomes after intensive VDT-PACE therapy for ... Methods: We identified 71 patients who received VDTPACE for relapsed MM, at Mayo Clinic from 7/2006 to 7/2012. Plasma cell leukemia was excluded. All data was ...

3. eviq.org.au eviq.org.au/haematology-and-bmt/multiple-myeloma/64-dt-pace-dexamethasone-thalidomide-cisplatin-do

64-DT-PACE (dexamethasone thalidomide ciSplatin ... Consider a starting dose of thalidomide 100 mg daily and increase as tolerated. Thalidomide may be dose reduced or omitted.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265019302976

Retrospective Review of the Use of High-Dose ... We report our experience with the high-dose chemotherapy mCBAD (modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone) regimen in newly ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9667441/

VTd-PACE and VTd-PACE-like regimens are effective salvage ... Overall response rate (ORR) is low, with a recent real-world study showing an ORR of only 20% to the subsequent applied therapy for triple-class ...

6. seer.cancer.gov seer.cancer.gov/seertools/seerrx/rx/53c44b1b102c1290262dd7e6/

Drugs for VDT-PACE - SEER - National Cancer Institute VDT-PACE ; Etoposide · Dom-Etoposide · EPEG. VP-16. VP-16-213 ; Thalidomide · K-17 · None ; Doxorubicin · 14-hydroxy-daunomycin · ADM. ADR. ADRI ; Cisplatin · Cis-Platin.