Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation
|Multiple Myeloma||Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase IIb, Multicenter, Open-Label, Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free)for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation|
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day +100 ]
- Mucositis Severity according to World Health Organization Scoring System [ Time Frame: Until Day +30 ]
- Mouth Pain Scores according to a Visual Analog Scale [ Time Frame: Until Day +30 ]
- Treatment Related Mortality [ Time Frame: Up to Day +100 ]
- MM response according to International Myeloma Working Group (IMWG) criteria. [ Time Frame: At the Day +100 visit ]
- Myeloablation [ Time Frame: Up to Day +30 ]Absolute neutrophil count (ANC) <0.5 × 109/L, absolute lymphocyte count (ALC) <0.1 × 109/L, platelet count <20,000/mm3, or bleeding requiring transfusion.
- Neutrophil engraftment [ Time Frame: Up to Day +100 ]ANC >0.5 × 109/L × first 3 consecutive daily assessments
- Platelet engraftment [ Time Frame: Up to Day +100 ]Untransfused platelet measurement >20,000/mm3 × first 3 consecutive daily assessments
- Non-engraftment [ Time Frame: Up to Day +100 ]Failure to reach an ANC >0.5 × 109/L × 3 consecutive daily assessments by Day +100.
|Study Start Date:||December 2012|
|Study Completion Date:||August 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days).
Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
200 mg melphalan/m2 will be divided into two separate, consecutive doses of 100 mg/m2 administered on day -3 and day -2 prior to ASCT. The High-Dose Melphaln HCL for Injection (Propylene Glycol-Free) will be reconstituted to 5 mg/mL (also containing 270 mg/mL of Captisol®). The Melphalan HCL for Injection (Propylene Glycol Free) will be further diluted with normal saline to a concentration of no greater than 0.45 mg/mL and infused over 30 minutes ( + or - 3 minutes)via a central venous catheter.
The sponsor of the current study, Ligand Pharmaceuticals Inc. (Ligand), previously CyDex Pharmaceuticals, Inc. (CyDex), is developing Melphalan HCL for Injection (Propylene Glycol-Free) as an orphan drug product for use as a high dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation. This new injectable form of melphalan HCL incorporates Captisol®, β cyclodextrin sulfobutyl ether sodium salts (also known as [SBE]7m-β-CD), into the product. Captisol is present to facilitate the use of an all aqueous diluent (normal saline) for reconstitution and administration of the freeze-dried product in place of the propylene glycol-ethanol diluent necessary for the currently used melphalan intravenous product. Captisol provides for solubilization and improved stability of the all aqueous reconstituted and diluted infusion solution.
This is the second of two studies supporting product registration. This study will be a multicenter study of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) conducted in 60 patients who have symptomatic MM and qualify for autologous stem cell transplantation (ASCT).
During the Study Period, patients will receive 100mg/m2 of either Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and on Day -2 for a total dose of 200mg/m2. Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints post infusion) drawn in a subset of patients on the second day of melphalan administration (Day -2).
Following one day of rest after the high dose myeloablative conditioning (Day -1), patients will receive an autologous graft (Day 0).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01660633
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|United States, Kansas|
|University of Kansas Medical Center|
|Fairway, Kansas, United States, 66205|
|United States, Massachusetts|
|University of Massachusetts|
|Worcester, Massachusetts, United States, 01655|
|United States, Missouri|
|Washington University School of Medicine|
|St Louis, Missouri, United States, 63110|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Medical College of Wisconsin/Froedtert Hospital|
|Milwaukee, Wisconsin, United States, 53226|
|Study Director:||Tim Freeman||Clinipace Worldwide|