Trial Outcomes & Findings for Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients (NCT NCT02994784)

NCT ID: NCT02994784

Last Updated: 2023-05-24

Results Overview

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.).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: 100 days
• Results posted on: 2023-05-24

Participant Flow

Participant milestones

Measure	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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Enrolled STARTED	27
Enrolled COMPLETED	27
Enrolled NOT COMPLETED	0
6 Months Follow-up STARTED	27
6 Months Follow-up COMPLETED	24
6 Months Follow-up NOT COMPLETED	3
12 Month Follow-up STARTED	24
12 Month Follow-up COMPLETED	24
12 Month Follow-up NOT COMPLETED	0

Reasons for withdrawal

Measure	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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
6 Months Follow-up Lost to Follow-up	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	20 Participants n=5 Participants
Race/Ethnicity, Customized Black	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Region of Enrollment United States	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days

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.).

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Number of Participants With Renal Dysfunction	2 Participants

PRIMARY outcome

Timeframe: 100 days

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).

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Number of Participants With Cardiac Dysfunction (New Arrhythmia)	5 Participants

SECONDARY outcome

Timeframe: 3 weeks

time to neutrophil engraftment

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Neutrophil Engraftment	10 days Interval 8.0 to 14.0

SECONDARY outcome

Timeframe: 100 days

Assess time to platelet engraftment

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Platelet Engraftment	17 days Interval 14.0 to 27.0

SECONDARY outcome

Timeframe: 100 days

Number of patients who expire within 100 days of transplant

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Treatment Related Mortality	0 Participants

SECONDARY outcome

Timeframe: 6 months

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

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Hematologic Overall Response Rate	22 Participants

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Measure	Evomela n=24 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Organ Response	13 Participants

SECONDARY outcome

Timeframe: 100 days

Number of participants with peri-transplant hospitalizations

Outcome measures

Measure	Evomela n=27 Participants 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Participants With Peri-transplant Hospitalizations	23 Participants

Adverse Events

Evomela

Serious events: 20 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Evomela n=27 participants at risk 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Cardiac disorders Cardiac arrhythmias	14.8% 4/27 • Number of events 4 • 12 months
Renal and urinary disorders Renal dysfunction	7.4% 2/27 • Number of events 2 • 12 months
Nervous system disorders Autonomic dysfunction	51.9% 14/27 • Number of events 14 • 12 months

Other adverse events

Measure	Evomela n=27 participants at risk 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 Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Gastrointestinal disorders Diarrhea	92.6% 25/27 • Number of events 25 • 12 months
Gastrointestinal disorders Nausea	74.1% 20/27 • Number of events 20 • 12 months
General disorders Fatigue	81.5% 22/27 • Number of events 22 • 12 months

Additional Information

John M Sloan, MD

Boston Medical Center and BU School of Medicine

Phone: 617-638-7519

Email: mark.sloan@bmc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place