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

Primary Purpose

Amyloidosis; Systemic

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Propylene Glycol-Free Melphalan Hydrochloride
Sponsored by
Boston Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloidosis; Systemic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Boston Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Evomela

Arm Description

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

Outcomes

Primary Outcome Measures

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.).
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).

Secondary Outcome Measures

Neutrophil Engraftment
time to neutrophil engraftment
Platelet Engraftment
Assess time to platelet engraftment
Treatment Related Mortality
Number of patients who expire within 100 days of transplant
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
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.
Participants With Peri-transplant Hospitalizations
Number of participants with peri-transplant hospitalizations

Full Information

First Posted
November 18, 2016
Last Updated
May 22, 2023
Sponsor
Boston Medical Center
Collaborators
Spectrum Pharmaceuticals, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02994784
Brief Title
Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Slow Accrual during COVID pandemic, alternative treatments available. Study halted early.
Study Start Date
January 8, 2018 (Actual)
Primary Completion Date
July 1, 2022 (Actual)
Study Completion Date
July 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Medical Center
Collaborators
Spectrum Pharmaceuticals, Inc

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis; Systemic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Evomela
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Propylene Glycol-Free Melphalan Hydrochloride
Other Intervention Name(s)
Evomela
Intervention Description
Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Primary Outcome Measure Information:
Title
Number of Participants With Renal Dysfunction
Description
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.).
Time Frame
100 days
Title
Number of Participants With Cardiac Dysfunction (New Arrhythmia)
Description
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).
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Neutrophil Engraftment
Description
time to neutrophil engraftment
Time Frame
3 weeks
Title
Platelet Engraftment
Description
Assess time to platelet engraftment
Time Frame
100 days
Title
Treatment Related Mortality
Description
Number of patients who expire within 100 days of transplant
Time Frame
100 days
Title
Hematologic Overall Response Rate
Description
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
Time Frame
6 months
Title
Organ Response
Description
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.
Time Frame
12 months
Title
Participants With Peri-transplant Hospitalizations
Description
Number of participants with peri-transplant hospitalizations
Time Frame
100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M Sloan, MD
Organizational Affiliation
Attending Physician
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There are no plans to share individual participant data.
Citations:
PubMed Identifier
23091105
Citation
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.
Results Reference
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Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients

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