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

Phase 2

Terminated

Conditions: Amyloidosis; Systemic

Interventions: Drug: Propylene Glycol-Free Melphalan Hydrochloride

Registration Number: NCT02994784

Lead Sponsor: Boston Medical Center

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 27

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evomela	Propylene Glycol-Free Melphalan Hydrochloride	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Renal Dysfunction	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.).
Number of Participants With Cardiac Dysfunction (New Arrhythmia)	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).

Secondary Outcome Measures

Name	Time	Method
Neutrophil Engraftment	3 weeks	time to neutrophil engraftment
Platelet Engraftment	100 days	Assess time to platelet engraftment
Treatment Related Mortality	100 days	Number of patients who expire within 100 days of transplant
Hematologic Overall Response Rate	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
Organ Response	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.
Participants With Peri-transplant Hospitalizations	100 days	Number of participants with peri-transplant hospitalizations