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

A Phase II Single-Center, Open-Label, Safety and Efficacy Study of Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation

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.

Study Overview

• Status: Terminated
• Conditions: Amyloidosis; Systemic
• Intervention / Treatment: Drug: Propylene Glycol-Free Melphalan Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Propylene Glycol-Free Melphalan Hydrochloride; Intravenous Propylene Glycol-Free Melphalan Hydrochloride; Other Names: Evomela

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Engraftment	time to neutrophil engraftment	3 weeks
Platelet Engraftment	Assess time to platelet engraftment	100 days
Treatment Related Mortality	Number of patients who expire within 100 days of transplant	100 days
Hematologic Overall Response Rate	Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): >50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD	6 months
Organ Response	Number of patients with organ response based on Gertz criteria (below); Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is > to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to < 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.; Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.	12 months
Participants With Peri-transplant Hospitalizations	Number of participants with peri-transplant hospitalizations	100 days

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: Spectrum Pharmaceuticals, Inc
• Investigators: Principal Investigator: John M Sloan, MD, Attending Physician

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2018
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 16, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Paraproteinemias; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: H-35835

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no plans to share individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No