Melphalan for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Unstable angina, Heart failure, Pregnancy, Nonhematologic malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

46 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Captisol Enabled Melphalan for treating multiple myeloma?

Melphalan flufenamide, a similar drug, showed effectiveness in treating relapsed/refractory multiple myeloma by improving progression-free survival when combined with dexamethasone, although it did not improve overall survival compared to another treatment. Additionally, high-dose melphalan is a standard treatment for multiple myeloma in patients undergoing stem cell transplantation, indicating its effectiveness in this context. ^{1 2 3 4 5}

Is melphalan safe for treating multiple myeloma?

Melphalan, often used with prednisone, has been a standard treatment for multiple myeloma and is generally considered safe, though it can have side effects. Studies have shown that adding other drugs like thalidomide can improve outcomes, but safety profiles should be discussed with a healthcare provider. ^{6 7 8 9 10}

What makes Captisol Enabled Melphalan unique for treating multiple myeloma?

Captisol Enabled Melphalan is a novel formulation of melphalan that uses a special carrier to improve its delivery and reduce side effects, potentially offering a more effective treatment option for multiple myeloma compared to traditional melphalan therapies. ^{2 4 11 12 13}

What is the purpose of this trial?

Captisol Enabled Melphalan, is a new formulation of the standard of care melphalan chemotherapy that in packaged in an inactive substance that is believed to help the chemotherapy be more stable (meaning that it doesn't lose its effect or need to be administered quickly after being mixed). It may also have fewer side effects such as problems with important levels of body electrolytes such as potassium, phosphorous and magnesium; and cause less kidney and heart damage\] than standard formulation melphalan. The purpose of this study is to determine if the investigators can achieve a certain level of Captisol Enabled Melphalan that would be best to use in treating Multiple Myeloma and AL Amyloidosis.

Research Team

Heather Landau, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults aged 18-75 with Multiple Myeloma or AL Amyloidosis who are undergoing an autologous transplant and have responded to prior chemotherapy. They must have adequate organ function, a certain number of cells available for transplant, and agree to avoid pregnancy. Excluded are those with recent heart issues, severe heart failure, other cancers within 3 years (with some exceptions), known allergies to the study drugs, or unsuitable conditions as determined by physicians.

Inclusion Criteria

I have shown improvement in my condition after initial treatment for myeloma.

My last cancer treatment showed some positive response.

I am willing to prevent pregnancy or fathering children during the trial.

Exclusion Criteria

Pregnant or lactating females

I haven't had cancer besides blood cancer in the last 3 years.

I haven't had recent severe heart issues or uncontrolled heart conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Test Dose CE Melphalan 10mg/m2 with PK studies Day -12 to Day-3, CE Melphalan Dose of Target AUC 13 mg/L/h infused with PK studies Day -2

2 weeks

Multiple visits for PK studies

Transplantation

3-10 x 10^6 CD 34+ cells/kg reinfused Day 0, Pegfilgrastim 6mg injection Day +1

1 week

Inpatient stay for transplantation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12-14 weeks

Regular follow-up visits

Treatment Details

Interventions

• Captisol Enabled Melphalan

Trial Overview The trial is testing Captisol Enabled Melphalan—a new formulation of melphalan chemotherapy thought to be more stable and potentially less harmful to kidneys and heart—alongside Pegfilgrastim support during autologous hematopoietic progenitor cell transplant. The goal is finding the optimal level of this drug for treating Multiple Myeloma and AL Amyloidosis.

Participant Groups

Group I: Melphalan Experimental Treatment 3 Interventions

Test Dose CE Melphalan 10mg/m2 with PK studies Day -12 to Day-3, CE Melphalan Dose of Target AUC 13 mg/L/h infused with PK studies Day -2, 3-10 x 10\^6 CD 34+ cells/kg reinfused Day 0, Pegfilgrastim 6mg injection Day +1

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Spectrum Pharmaceuticals, Inc

Industry Sponsor

Trials

83

Recruited

8,200+

Tom Riga

Spectrum Pharmaceuticals, Inc

Chief Executive Officer since 2021

Bachelor's degree in Business Administration from the University of Rhode Island

Francois Lebel

Spectrum Pharmaceuticals, Inc

Chief Medical Officer since 2018

MD from McGill University

Findings from Research

In the OCEAN study, melphalan flufenamide (melflufen) showed similar progression-free survival (PFS) and overall survival (OS) compared to pomalidomide in 153 patients with relapsed/refractory multiple myeloma who were refractory to prior alkylators.

Among patients with a longer time to progression (TTP ≥ 36 months) after prior autologous stem cell transplantation, melflufen demonstrated longer median PFS and OS compared to pomalidomide, indicating its potential effectiveness in a specific subgroup of alkylator-refractory patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melflufen in relapsed/refractory multiple myeloma refractory to prior alkylators: A subgroup analysis from the OCEAN study. Schjesvold, FH., Ludwig, H., Mateos, MV., et al.[2023]

A study involving 63 multiple myeloma patients showed that the pharmacokinetics (PK) of generic melphalan (MEL) is comparable to that of the innovator formulation, indicating that both formulations behave similarly in the body.

Clinical outcomes, such as the severity of mucositis and the time to neutrophil and platelet engraftment, were not significantly different between patients receiving generic and innovator MEL, suggesting that the generic version is equally effective for autologous stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Efficacy of Generic Melphalan Is Comparable to Innovator Formulation in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplantation. Pai, AA., Devasia, AJ., Panetta, JC., et al.[2022]

In a study comparing lenalidomide-dexamethasone (len/dex) and melphalan-prednisone-lenalidomide (MPR) in 89 elderly patients with myeloma, both treatments showed similar efficacy in terms of time to progression, progression-free survival, and overall survival, indicating that either regimen can be effective for this patient group.

However, MPR was associated with significantly higher rates of severe hematologic toxicities, such as neutropenia and thrombocytopenia, suggesting that while both treatments are effective, len/dex may be a safer option with fewer severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. Gay, F., Vincent Rajkumar, S., Falco, P., et al.[2018]

In a study of 75 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib and dexamethasone (Kd56) showed a 60% overall response rate and a median progression-free survival (PFS) of 10 months, indicating its efficacy in a real-world clinical setting.

The treatment was well tolerated, with a low rate of adverse events, including no cases of neuropathy and only 10% of patients experiencing cardiovascular events above grade 3, suggesting a favorable safety profile for elderly and heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: A retro-prospective observational study. Del Giudice, ML., Gozzetti, A., Antonioli, E., et al.[2023]

In a study of 1162 multiple myeloma patients, those treated with the combination of thalidomide, melphalan, and prednisone (MPT) showed significantly better overall survival (OS) rates compared to those treated with melphalan and prednisone (MP) alone, with median OS of 4.2 years for MPT versus 2.2 years for MP in the first line of treatment.

The relative risk of death was reduced by 39% in the MPT group compared to the MP group in the first line of therapy, indicating that MPT is a more effective treatment option for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma--a retrospective population based study of 1162 patients. Lund, J., Uttervall, K., Liwing, J., et al.[2013]

Melphalan is a key treatment for multiple myeloma and ovarian cancer, with oral melphalan combined with prednisone being the standard therapy for elderly patients since the 1960s.

Recent advancements in understanding drug resistance have led to the development of novel therapies like thalidomide, lenalidomide, and bortezomib, which can enhance the effectiveness of melphalan and change treatment approaches for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan and its role in the management of patients with multiple myeloma. Falco, P., Bringhen, S., Avonto, I., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Melflufen in relapsed/refractory multiple myeloma refractory to prior alkylators: A subgroup analysis from the OCEAN study. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Melphalan flufenamide for relapsed/refractory multiple myeloma. [2022]

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

Lenalidomide plus melphalan without prednisone for previously untreated older patients with multiple myeloma: a phase II trial. [2018]

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

Pharmacokinetics and Efficacy of Generic Melphalan Is Comparable to Innovator Formulation in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplantation. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide. [2023]

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

Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. [2018]

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

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: A retro-prospective observational study. [2023]

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

Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma--a retrospective population based study of 1162 patients. [2013]

9. Italy pubmed.ncbi.nlm.nih.gov

Safety of leflunomide plus infliximab combination therapy in rheumatoid arthritis. [2018]

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

Intravenous meloxicam for the treatment of moderate to severe acute pain: a pooled analysis of safety and opioid-reducing effects. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Melphalan and its role in the management of patients with multiple myeloma. [2020]

12. Italy pubmed.ncbi.nlm.nih.gov

Intermediate-dose (25mg/m2) IV melphalan for multiple myeloma with renal failure. [2013]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies-Current Research and Clinical Approaches. [2021]