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

Amyloidosis; Systemic Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02994784
• Other study ID #: H-35835
• Status: Terminated
• Phase: Phase 2
• Start date: January 8, 2018
• Est. completion date: July 1, 2022

Study information

• Verified date: May 2023
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: July 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Amyloidosis; Systemic
• Immunoglobulin Light-chain Amyloidosis

Intervention

Drug:
• Propylene Glycol-Free Melphalan Hydrochloride
Intravenous Propylene Glycol-Free Melphalan Hydrochloride

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Medical Center	Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Neutrophil Engraftment	time to neutrophil engraftment	3 weeks
Secondary	Platelet Engraftment	Assess time to platelet engraftment	100 days
Secondary	Treatment Related Mortality	Number of patients who expire within 100 days of transplant	100 days
Secondary	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
Secondary	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
Secondary	Participants With Peri-transplant Hospitalizations	Number of participants with peri-transplant hospitalizations	100 days