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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new version of the chemotherapy drug melphalan, designed to be more stable and potentially cause fewer side effects for people with multiple myeloma or AL amyloidosis. Researchers aim to determine if this new formulation, known as Captisol Enabled Melphalan, is more effective and safer than the standard version. The trial seeks individuals with multiple myeloma or AL amyloidosis who have shown some positive response to prior treatments. Those who have experienced improvements with previous chemotherapy and meet other health criteria might be a good fit for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new formulation.

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.

Is there any evidence suggesting that Captisol Enabled Melphalan is likely to be safe for humans?

Research has shown that Captisol Enabled Melphalan, a new version of the drug melphalan, is safe for use. Studies have found that this version, known as EVOMELA, is safe even for individuals with serious kidney problems. It is formulated without propylene glycol, a common drug ingredient that can cause side effects. This new version aims to be gentler on the kidneys and heart compared to regular melphalan. Previous users have tolerated it well, and it may cause fewer issues with essential body minerals like potassium and magnesium. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often rely on conventional chemotherapy drugs, Captisol Enabled Melphalan is unique due to its delivery method and formulation. This treatment uses a special formulation that enhances the solubility and stability of melphalan, potentially leading to more effective drug delivery and reduced side effects. Researchers are excited about Captisol Enabled Melphalan because it aims to achieve a targeted drug exposure, which may improve the therapeutic outcomes while minimizing toxicity. This innovative approach could offer a promising new option for patients with multiple myeloma, potentially improving their quality of life and treatment experience.

What evidence suggests that Captisol Enabled Melphalan might be an effective treatment for Multiple Myeloma?

Studies have shown that Captisol Enabled Melphalan, the treatment tested in this trial, effectively treats multiple myeloma. This new version of the drug performs as well as standard melphalan. Research suggests it may better prepare patients for stem cell transplants by increasing the drug's stability, potentially reducing side effects. This formulation lacks propylene glycol, which might lower the risk of kidney and heart problems. Overall, Captisol Enabled Melphalan shows promise for safety and effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Heather Landau, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26327631/

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy ... This study confirms the efficacy and acceptable safety profile of EVOMELA, a new propylene glycol-free melphalan formulation, as a high-dose conditioning ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2016/207155Orig1s000_Orig2s000MedR.pdf

MEDICAL REVIEW(S) - accessdata.fda.gov Overall,. CE-Melphalan HCl was effective in preparing symptomatic multiple myeloma patients for ASCT. Regulatory Recommendation for Safety ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1083879115005741

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy ... ... Captisol-enabled melphalan formulation is bioequivalent to Alkeran. ... High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a ...

4. investor.ligand.com investor.ligand.com/news-and-events/press-releases/news-details/2012/Ligand-Initiates-Pivotal-Trial-of-Captisol-Enabled-Propylene-Glycol-Free-Melphalan-in-Patients-with-Multiple-Myeloma-12-10-2012/default.aspx

Ligand Initiates Pivotal Trial of Captisol-Enabled®, ... This multi-center trial will evaluate safety and efficacy in 60 patients, and is intended to confirm the results from an earlier Phase 2 study ...

5. withpower.com withpower.com/trial/phase-1-amyloidosis-8-2016-2c6f5

Melphalan for Multiple Myeloma · Info for Participants Melphalan flufenamide, a similar drug, showed effectiveness in treating relapsed/refractory multiple myeloma by improving progression-free survival when ...

6. captisol.com captisol.com/technology

Technology Two decades of patient experience and recent data have shown that Captisol is safe, even in patients with severe renal impairment. Clinical studies were ...

7. astctjournal.org astctjournal.org/article/S1083-8791(15)00574-1/fulltext

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy ... This study confirms the efficacy and acceptable safety profile of EVOMELA, a new propylene glycol-free melphalan formulation, as a high-dose conditioning ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/15/NCT02669615/Prot_000.pdf

Standard non-CTD Styles Template The high-dose melphalan clinical data found in the public domain support the conduct of well-controlled clinical trials with melphalan for high-dose.