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

NCT ID: NCT02994784

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-08
• Study Completion Date: 2022-07-01

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.

Detailed Description

After giving written informed consent, subjects will be evaluated for eligibility for enrollment in the study. Baseline evaluations will be performed as outlined in Section 7. Subjects who satisfy all inclusion and exclusion criteria will begin the study drug. Subjects will be monitored from the time of the medication administration until discharge from the transplant program for safety. Organ function and hematologic status will also be measured at 6 and 12 month follow-up visits.

Standard response criteria for AL amyloidosis hematologic and organ response will be used. Overall response rate will be measured and participants will be categorized into complete response, very good partial response, partial response and progressive disease. Progression free survival, organ response, and safety and tolerability of propylene glycol-free melphalan hydrochloride will be assessed.

Conditions

Amyloidosis; Systemic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Evomela

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

Group Type: EXPERIMENTAL

Propylene Glycol-Free Melphalan Hydrochloride

Intervention Type: DRUG

Intravenous Propylene Glycol-Free Melphalan Hydrochloride

Interventions

Propylene Glycol-Free Melphalan Hydrochloride

Intravenous Propylene Glycol-Free Melphalan Hydrochloride

Intervention Type: DRUG

Other Intervention Names

Evomela

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John M Sloan, MD

Role: PRINCIPAL_INVESTIGATOR

Attending Physician

Locations

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23091105 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37607644 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

H-35835

Identifier Type: -

Identifier Source: org_study_id