Safety & Efficacy Study High Dose Evomela Injection for MA Conditioning in MM Patients With Autologous Transplantation
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|ClinicalTrials.gov Identifier: NCT01660633|
Recruitment Status : Completed
First Posted : August 9, 2012
Last Update Posted : February 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)||Phase 2|
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 Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||December 2012|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||August 2014|
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.
Other Name: Evomela, Alkeran
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day +100 ]AE coding will be performed using the MedDRA Version 11.0 or greater. The severity of the toxicities will be graded according to the NCI CTCAE Version 4.0 whenever possible. AEs occurring when treatment starts on Day -3 through Day + 100 will be recorded in the AE section of the eCRF and causality will be assigned by the Principal Investigator.
- Mucositis Severity according to World Health Organization Scoring System [ Time Frame: Until Day +30 ]The baseline measurement will be the last assessment prior to receiving the first dose of study treatment. The on-treatment period will be defined as the day after the first dose of study treatment to 30 days after the last dose of study treatment. The incidence of severe mucositis (WHO Grade 3 or 4) will be summarized by frequencies and percentages. In addition, the incidence of oral mucositis will be summarized by WHO grade. Time from start of the first dose of study medication to peak oral mucositis score will also be calculated.
- Mouth Pain Scores according to a Visual Analog Scale [ Time Frame: Until Day +30 ]Baseline VAS for mouth pain and dysphagia will be the VAS score collected prior to receiving the first dose of study medication. Analyses of changes and/or percent changes from baseline in the VAS scores will be analyzed for each time point collected during the 30 day on-treatment period. The minimum and maximum VAS scores during the 30 day on-treatment period will also be calculated for mouth pain and dysphagia, and the time to the minimum and maximum VAS scores will be summarized descriptively.
- Treatment Related Mortality [ Time Frame: Up to Day +100 ]TRM, which is defined as death not due to disease progression before Day +90/+100, will be calculated. This outcome measure will be summarized by the cumulative incidence estimated with 95% confidence intervals.
- MM response according to International Myeloma Working Group (IMWG) criteria. [ Time Frame: At the Day +100 visit ]Definition of active MM, clonal bone marrow plasma cells >10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder and one or more biomarkers of malignancy (MDEs) defined in the criteria.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|
|Saint 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|