Melphalan + Prednisone + Thalidomide/Lenalidomide for Multiple Myeloma

Recruiting at 444 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Aspirin, Heparin, Coumadin

Disqualifiers: Uncontrolled hypertension, Congestive heart failure, Angina, Cardiac arrhythmia, Psychiatric illness, 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: 15

306 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies melphalan and prednisone with thalidomide to see how well it works compared to melphalan and prednisone together with lenalidomide in treating patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as melphalan and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Thalidomide and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It is not yet known whether melphalan and prednisone are more effective when given together with thalidomide or lenalidomide in treating multiple myeloma.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you can continue taking bisphosphonates or growth factors like erythropoietin, although erythropoietin is discouraged due to increased risk of blood clots with thalidomide or lenalidomide.

What data supports the effectiveness of the drug combination Melphalan, Prednisone, and Lenalidomide for treating multiple myeloma?

Research shows that the combination of Melphalan, Prednisone, and Lenalidomide (MPR) has significant activity against multiple myeloma, especially in newly diagnosed patients. Lenalidomide, a key component, has been shown to improve outcomes when added to traditional treatments, although it may increase side effects. ^{1 2 3 4 5}

Is the combination of Melphalan, Prednisone, and Lenalidomide/Thalidomide safe for treating multiple myeloma?

The combination of Melphalan, Prednisone, and Lenalidomide/Thalidomide has been used to treat multiple myeloma, but it can cause side effects like neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and in rare cases, intrahepatic cholestasis (liver condition). While Lenalidomide is considered more effective and potentially less toxic than Thalidomide, it still requires careful monitoring for these side effects. ^{2 3 5 6 7}

What makes the drug combination of Melphalan, Prednisone, Thalidomide, and Lenalidomide unique for treating multiple myeloma?

This drug combination is unique because it combines the standard treatment of melphalan and prednisone with thalidomide and lenalidomide, which are known for their immunomodulatory effects (they help the immune system fight cancer). Lenalidomide, a derivative of thalidomide, is considered more effective and potentially less toxic, offering a promising option for newly diagnosed multiple myeloma patients, especially those who are elderly. ^{2 3 8 9 10}

Research Team

Alexander K Stewart

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with newly diagnosed multiple myeloma. Eligible participants are those over 65 who declined alternative treatments, or adults under 65 not suitable for stem cell transplantation. They must have an ECOG performance status of <=2, no severe peripheral neuropathy, uncontrolled illnesses, active infections, or recent malignancies (with exceptions). Women of childbearing age must test negative for pregnancy and follow strict birth control measures.

Inclusion Criteria

I have myeloma and haven't been treated for it, except for short-term specific medications.

I am willing to use a condom during and after treatment as required.

I am over 65 and have declined other treatments, or I am 18-64, cannot have a stem cell transplant, or have declined it.

Exclusion Criteria

I do not have smoldering myeloma or MGUS without symptoms.

I do not have any severe illnesses that would stop me from following the study's requirements.

You have had Stevens Johnson syndrome before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive melphalan and prednisone with either thalidomide or lenalidomide. Treatment repeats every 28 days for up to 12 courses.

336 days (12 cycles of 28 days each)

12 visits (in-person)

Maintenance Therapy

Patients continue to receive thalidomide or lenalidomide in the absence of disease progression.

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

10 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

Treatment Details

Interventions

• Lenalidomide
• Melphalan
• Prednisone
• Thalidomide

Trial Overview The study compares two treatment combinations: melphalan and prednisone with thalidomide versus the same chemotherapy drugs with lenalidomide. The goal is to determine which combination better halts cancer growth by either killing cells or blocking blood flow to them. Participants will be randomly assigned to one of these treatment groups.

Participant Groups

Group I: Arm II (lenalidomide) Experimental Treatment 4 Interventions

INDUCTION THERAPY: Patients receive melphalan PO and prednisone PO QD on days 1-4, and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive lenalidomide PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression.

Group II: Arm I (thalidomide) Active Control 5 Interventions

INDUCTION THERAPY: Patients receive melphalan PO and prednisone PO QD on days 1-4, and thalidomide PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive thalidomide PO QD and continue in the absence of disease progression.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 54 newly diagnosed elderly multiple myeloma patients, the combination of melphalan, prednisone, and lenalidomide (MPR) resulted in a high response rate, with 81% of patients achieving at least a partial response and 23.8% achieving a complete response.

The treatment showed excellent safety profiles, with manageable hematologic adverse events, and a remarkable 1-year overall survival rate of 100%, indicating that MPR is a promising first-line therapy for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. Palumbo, A., Falco, P., Corradini, P., et al.[2020]

The combination treatment of melphalan, prednisone, and lenalidomide (MPR) shows significant antimyeloma activity in newly diagnosed multiple myeloma patients, with a median progression-free survival of 28.5 months and a 2-year overall survival rate of 91%.

While MPR treatment resulted in manageable hematologic side effects, including grade 3/4 neutropenia in 52% of patients and grade 3/4 thrombocytopenia in 24%, no serious bleeding complications were reported, indicating that the regimen is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Palumbo, A., Falco, P., Falcone, A., et al.[2018]

Lenalidomide has shown significant clinical activity in treating multiple myeloma, improving response rates to induction therapy to 85-95% in previously untreated patients, compared to older regimens that had response rates of only 45-55%.

Unlike thalidomide, lenalidomide aims to enhance efficacy while reducing side effects, making it a promising option for patients with newly diagnosed or relapsed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. Thomas, SK., Richards, TA., Weber, DM.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

lenalidomide (REVLIMID°) in untreated multiple myeloma. [2019]

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

Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. [2020]

3. 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]

4. France pubmed.ncbi.nlm.nih.gov

[Treatment of myeloma in the elderly]. [2018]

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

Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Lenalidomide induced intrahepatic cholestasis in newly diagnosed patients of multiple myeloma. [2021]

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

Thalidomide and its derivatives: new promise for multiple myeloma. [2017]

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

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

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

Continuous lenalidomide treatment for newly diagnosed multiple myeloma. [2022]