Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Propylene Glycol-Free Melphalan Hydrochloride
Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [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.), cardiac dysfunction (new arrhythmia), or autonomic dysfunction (decline in sitting systolic blood pressure of ≥20mm Hg compared to baseline)
Secondary Outcome Measures
- neutrophil engraftment [3 weeks]
time to neutrophil engraftment
- platelet engraftment [3 weeks]
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
- organ response [12 months]
Number of patients with organ response based on Gertz criteria
- number of hospitalizations [100 days]
Number of hospitalizations per patient
Eligibility Criteria
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
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Decompensated or uncontrolled heart failure
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
Sponsors and Collaborators
- Boston Medical Center
- Spectrum Pharmaceuticals, Inc
Investigators
- Principal Investigator: John M Sloan, MD, Attending Physician
Study Documents (Full-Text)
None provided.More Information
Publications
- H-35835