Autologous Stem Cell Transplant for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Craig Hofmeister, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Ritonavir

Disqualifiers: Cardiovascular disease, HIV, Hepatitis B, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 3 days

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the best dose and side effects of mephalan in treating patients with multiple myeloma who are undergoing stem cell transplant. Chemotherapy drugs, such as mephalan, 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. This trial uses a new method of dosing that is based on analysis of each individual's blood levels of melphalan after receiving a part of the dose, termed pharmacokinetic analysis. This may help to learn more about how to dose melphalan correctly and which patients are likely to benefit from a personalized dose.

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 your doctor to understand how your current medications might interact with the trial treatment.

What data supports the effectiveness of the treatment Melphalan in autologous stem cell transplant for multiple myeloma?

Research shows that high-dose melphalan followed by autologous stem cell transplantation is a standard and effective treatment for multiple myeloma, with studies confirming its efficacy and safety. A new formulation, EVOMELA, has shown high response rates and a good safety profile, making it a reliable option for patients undergoing this treatment. ^{1 2 3 4 5}

Is the autologous stem cell transplant with melphalan safe for humans?

The autologous stem cell transplant using melphalan, particularly the propylene glycol-free formulation called Evomela, has been shown to have an acceptable safety profile in humans. Studies report no treatment-related deaths and manageable side effects, such as low rates of severe mouth sores, making it generally safe for use in patients with multiple myeloma. ^{4 6 7 8 9}

How is the treatment with Melphalan for multiple myeloma unique?

The treatment with high-dose Melphalan followed by autologous stem cell transplantation is unique because it significantly increases the chances of complete remission and extends survival compared to standard chemotherapy, especially in patients who were previously not considered for transplantation, such as those with kidney issues. ^{1 2 5 10 11}

Research Team

Craig Hofmeister, MD, MPH

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with multiple myeloma who need treatment and can undergo stem cell transplant. They must have a certain level of blood cells, kidney function, liver function, heart health, and lung capacity. Women must not be pregnant or breastfeeding and agree to contraception. People with recent disease progression, serious infections or conditions that could affect the study are excluded.

Inclusion Criteria

Your lung function tests show that you can breathe well and your lungs are healthy.

My heart pumps well, with an ejection fraction of 45% or higher.

I have undergone at least two treatments for my condition as per IMWG guidelines.

Exclusion Criteria

I have a known heart condition.

You have shown signs of your disease getting worse or coming back between the time you were screened for the trial and the day you were supposed to receive melphalan treatment.

Known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive high dose melphalan IV on day -3 and PK-directed melphalan IV on day -1, followed by autologous stem cell transplantation on day 0

3 days

In-patient stay for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 7, 14, 30, 60, and 90 days

90 days

5 visits (in-person)

Treatment Details

Interventions

• Melphalan

Trial Overview The trial tests different doses of Melphalan chemotherapy in patients undergoing autologous stem cell transplantation for multiple myeloma. It aims to find the best dose by measuring how the drug behaves in the body (pharmacokinetics). Participants will also complete questionnaires about their experience.

Participant Groups

Group I: Treatment (Melphalan-based autologous transplant) Experimental Treatment 3 Interventions

Patients receive high dose (100 mg/m2) melphalan IV over 30 minutes on day -3 and PK-directed melphalan IV over 30 minutes on day -1 to achieve set cumulative melphalan exposure levels. Patients then undergo stem cell infusion on day 0.

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

Approved in European Union as Alkeran for:

• Multiple myeloma
• Malignant lymphoma
• Acute lymphoblastic leukemia
• Acute myeloblastic leukemia
• Childhood neuroblastoma
• Ovarian cancer
• Mammary adenocarcinoma

Approved in United States as Alkeran for:

• Multiple myeloma
• High-dose conditioning before hematopoietic stem cell transplant
• Uveal melanoma with unresectable hepatic metastases

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

High-dose melphalan followed by autologous stem cell transplantation (auto-SCT) is feasible and shows efficacy in elderly patients with multiple myeloma, with a complete response or very good partial response rate of 60%.

The median overall survival for elderly patients after auto-SCT was 40.8 months, which is promising, although lower than the 72.5 months observed in younger patients, indicating that while effective, further studies are needed to optimize treatment for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. Muta, T., Miyamoto, T., Fujisaki, T., et al.[2019]

High-dose melphalan is the preferred chemotherapy for autologous stem cell transplantation in multiple myeloma patients, supported by earlier randomized trials.

Alternative treatment regimens involving different combinations of drugs and radiation have not shown better results than high-dose melphalan alone, according to multiple published studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? Aljitawi, OS., McGuirk, JP.[2013]

Melphalan continues to be a key reference drug in treating multiple myeloma, used in combination with newer targeted therapies for both initial and salvage treatments.

The review highlights the evolution of treatment strategies, emphasizing the role of melphalan in both standard chemotherapy and stem cell transplantation for newly diagnosed or relapsed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan: old and new uses of a still master drug for multiple myeloma. Musto, P., D'Auria, F.[2019]

EVOMELA, a new formulation of melphalan that is free from propylene glycol, has been shown to be safe and effective for high-dose conditioning in autologous stem cell transplantation for multiple myeloma, with a 100% overall response rate in a study of 61 patients.

The study reported low incidences of severe side effects, such as grade 3 mucositis (10%) and stomatitis (5%), indicating that EVOMELA has an acceptable safety profile compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. Hari, P., Aljitawi, OS., Arce-Lara, C., et al.[2017]

Autologous stem cell transplant (ASCT) significantly improved outcomes for multiple myeloma (MM) patients, with an overall response rate of 80% and 64% survival rate over a 50-month follow-up period.

Patients who underwent ASCT in the early phase of MM showed better results, with a higher likelihood of achieving complete remission (CR) or very good partial remission (VGPR), which were predictive factors for longer overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous stem cell transplantation in the treatment of multiple myeloma--single center experience]. Marjanović, S., Stamatović, D., Tukić, L., et al.[2019]

In a study of 514 multiple myeloma patients, the propylene glycol-free formulation of melphalan (PGF-mel) showed similar efficacy to the conventional propylene glycol-based formulation (PG-mel) in terms of relapse rates after high-dose melphalan with autologous hematopoietic cell transplantation.

However, PGF-mel was associated with fewer severe adverse events like mucositis and febrile neutropenia, leading to a preference for PG-mel despite the potential benefits of PGF-mel, due to cost considerations and other factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Khan, AM., Yucebay, F., Zhao, Q., et al.[2023]

In a phase II study involving 24 patients with multiple myeloma, a single dose of 200 mg/m2 of Evomela (PG-Free Melphalan) was found to be safe and resulted in a high overall response rate of 96%, with 75% achieving a very good partial response.

The study revealed significant variability in pharmacokinetics (PK) among patients, indicating that some individuals had much higher drug exposure, suggesting that future research could focus on optimizing dosing strategies to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of High-Dose Propylene Glycol-Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation. Dhakal, B., D'Souza, A., Lakshman, A., et al.[2019]

Evomela™, a propylene-free formulation of melphalan, offers improved stability and avoids the potential side effects associated with propylene glycol, making it a safer option for patients undergoing autologous stem cell transplantation for multiple myeloma.

The review highlights the pharmacokinetics and clinical data supporting the use of Evomela™ in myeloma treatment, indicating its effectiveness in ensuring proper dose delivery during transplantation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propylene glycol-free melphalan as conditioning regimen for autologous transplantation in myeloma. Aljitawi, OS., Hari, P.[2020]

Melphalan, the first treatment for multiple myeloma, has evolved from a median survival of 2-3 years to improved outcomes through intensified dosing (140-200 mg/m²) and support with autologous stem cell transplants to reduce severe side effects like myelosuppression.

New treatment options, including angiogenesis inhibitors, proteasome inhibitors, and immunotherapy, are being explored to enhance the efficacy of multiple myeloma therapies, offering additional mechanisms to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of myeloma: recent developments. Zweegman, S., Huijgens, PC.[2019]

High-dose melfalan chemotherapy followed by autologous blood stem cell transplantation significantly increases the chances of achieving complete remission and extends survival in patients with multiple myeloma compared to traditional chemotherapy.

Recent studies suggest that patients with multiple myeloma and renal insufficiency can also benefit from stem cell transplantation, as demonstrated by the first successful case reported in this study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous transplantation of peripheral hematopoietic cells in a patient with multiple myeloma and renal insufficiency]. Krejcí, M., Doubek, M., Adam, Z., et al.[2013]

High-dose melphalan (HD-Mel) is a safe and effective preparative regimen for autologous stem cell transplantation (ASCT) in patients with relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), showing a 36-month overall survival rate of 71% with no transplant-related mortality.

The efficacy of HD-Mel was found to be non-inferior to traditional BEAM-like regimens, with similar event-free survival rates, indicating that HD-Mel can be a viable alternative for patients receiving non-frozen stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma. Fernández-Gutiérrez, JA., Reyes-Cisneros, OA., Litzow, MR., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? [2013]

3. England pubmed.ncbi.nlm.nih.gov

Melphalan: old and new uses of a still master drug for multiple myeloma. [2019]

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

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. [2017]

5. Serbia pubmed.ncbi.nlm.nih.gov

[Autologous stem cell transplantation in the treatment of multiple myeloma--single center experience]. [2019]

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

Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. [2023]

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

Pharmacokinetics of High-Dose Propylene Glycol-Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation. [2019]

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

Propylene glycol-free melphalan as conditioning regimen for autologous transplantation in myeloma. [2020]

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

Treatment of myeloma: recent developments. [2019]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Autologous transplantation of peripheral hematopoietic cells in a patient with multiple myeloma and renal insufficiency]. [2013]

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

High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma. [2022]