Clinical trial NCT02994784: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Amyloidosis; Systemic
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: Spectrum Pharmaceuticals, Inc
First posted: 2016-12-16
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Renal Dysfunction
timeFrame: 100 days
measure: Number of Participants With Cardiac Dysfunction (New Arrhythmia)
timeFrame: 100 days
Secondary outcomes:
measure: Neutrophil Engraftment
timeFrame: 3 weeks
measure: Platelet Engraftment
timeFrame: 100 days
measure: Treatment Related Mortality
timeFrame: 100 days
measure: Hematologic Overall Response Rate
timeFrame: 6 months
measure: Organ Response
timeFrame: 12 months
measure: Participants With Peri-transplant Hospitalizations
timeFrame: 100 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
Study officials:
affiliation: Attending Physician
name: John M Sloan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.