Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients

NCT02994784 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: H-35835
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open label study designed to evaluate the safety and efficacy of propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell transplantation.

Conditions

Amyloidosis; Systemic

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Renal Dysfunction

  To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a \>/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to \>/=1.5 mg/dL for at least 2 days.).

  100 days

• Number of Participants With Cardiac Dysfunction (New Arrhythmia)

  To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).

  100 days

Secondary Outcomes (6)

• Neutrophil Engraftment

  3 weeks

• Platelet Engraftment

  100 days

• Treatment Related Mortality

  100 days

• Hematologic Overall Response Rate

  6 months

• Organ Response

  12 months

Study Arms (1)

Evomela

EXPERIMENTAL

Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation

Drug: Propylene Glycol-Free Melphalan Hydrochloride

Interventions

Propylene Glycol-Free Melphalan Hydrochloride DRUG

Intravenous Propylene Glycol-Free Melphalan Hydrochloride

Also known as: Evomela

Evomela

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Eastern Cooperative Oncology Group Performance Status 0-2
• Histologic diagnosis of primary systemic (AL) amyloidosis based on:
• Deposition of amyloid material by Congo red stain showing characteristic apple green birefringence AND
• Evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum or urine by immunofixation electrophoresis AND/OR abnormal serum free light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by immunohistochemistry, flow cytometry, or in situ hybridization AND
• Evidence of organ involvement
• Eligible for treatment with high dose melphalan and stem cell transplantation per institutional guidelines
• Ability to understand and willingness to sign informed consent
• Pulmonary Function Test demonstrating a diffusion capacity of lung for carbon monoxide ≥ 50%
• Left ventricular ejection fraction ≥40%
• Systolic blood pressure \>90 mm Hg (supine position)
• Eastern Cooperative Oncology Group Performance status of 2 or better (unless patient is diagnosed with AL amyloidosis involving the gastrointestinal and peripheral/autonomic nervous systems, then performance status of 3 is acceptable)

You may not qualify if:

• Previous high-dose melphalan and stem cell transplant
• Previous total cumulative dose of oral melphalan \> 300 mg
• Cytotoxic chemotherapy within the previous 28 days
• New York Heart Association ≥3
• Decompensated or uncontrolled heart failure
• Oxygen dependence
• epidermal growth factor receptor \< 30 ml/min
• Active infection (i.e HIV, Hepatitis B or C)
• Pregnancy or breastfeeding
• Exposure to another investigational drug within 3-4 weeks prior to start of study treatment
• Ongoing alcohol or drug addiction
• Unable or unwilling to comply with the protocol

Sponsors & Collaborators

• Boston Medical Center: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (2)

• Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.

  PMID: 23091105 BACKGROUND

• Sarosiek S, Lee MH, Doros G, Edwards CV, Quillen K, Brauneis D, Shelton AC, Sanchorawala V, Sloan JM. Safety and Efficacy of Propylene Glycol-Free Melphalan in Patients with AL Amyloidosis Undergoing Autologous Stem Cell Transplantation: Results of a Phase II Study. Transplant Cell Ther. 2023 Nov;29(11):695.e1-695.e7. doi: 10.1016/j.jtct.2023.08.018. Epub 2023 Aug 20.

  PMID: 37607644 DERIVED

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Study was halted early resulting in relatively small numbers of participants analyzed.

Results Point of Contact

• Title: John M Sloan, MD
• Organization: Boston Medical Center and BU School of Medicine

mark.sloan@bmc.org

617-638-7519

Study Officials

• John M Sloan, MD

  Attending Physician

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: December 16, 2016
• Study Start: January 8, 2018
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)