This trial is active, not recruiting.

Condition multiple myeloma
Treatment high-dose melphalan hcl for injection (propylene glycol-free)
Phase phase 2/phase 3
Sponsor Spectrum Pharmaceuticals, Inc
Collaborator Clinipace LTD
Start date December 2012
End date February 2014
Trial size 60 participants
Trial identifier NCT01660633, CDX-353-002


The purpose of this trial is to confirm the safety and efficacy of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) as a myeloablative conditioning regimen in multiple myeloma patients (MM) undergoing autologous transplantation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days).
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.

Primary Outcomes

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

Secondary Outcomes

MM response according to International Myeloma Working Group (IMWG) criteria.
time frame: At the Day +100 visit
time frame: Up to Day +30
Neutrophil engraftment
time frame: Up to Day +100
Platelet engraftment
time frame: Up to Day +100
time frame: Up to Day +100

Eligibility Criteria

Male or female participants up to 70 years old.

Inclusion Criteria: - Patients with symptomatic MM based on IMWG guidelines requiring treatment who are eligible for ASCT. - Patients who are 70 years of age or younger at time of transplant. Patients older than 70 years of age may be enrolled on a case-by-case basis if the patient meets local institutional criteria to receive a total melphalan dose of 200 mg/m2 as a conditioning regimen and if approved by the medical monitor. - Patients with an adequate autologous graft, defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based on patient body weight. Patients with adequate organ function as measured by: - Cardiac function: Left ventricular ejection fraction at rest >40% (documented within 8 weeks prior to Day -3). - Hepatic function: Bilirubin <2 × the upper limit of normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <3 × upper limit of normal. - Renal function: Creatinine clearance >40 mL/minute (measured or calculated/estimated). - Pulmonary function: Carbon monoxide diffusing capacity (DLCO)corrected for hemoglobin (Hgb), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC), and oxygen saturation >92% on room air (documented within 4 weeks prior to Day -3). - Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Exclusion Criteria: - Patients with smoldering MM not requiring therapy. - Patients with plasma cell leukemia. - Patients with systemic amyloid light chain amyloidosis. - Patients with uncontrolled hypertension. - Patients with an active bacterial, viral, or fungal infection. - Patients with a life expectancy of < 6 months. - Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent >5 years previously will be allowed. Cancer treated with curative intent <5 years previously will not be allowed unless approved by the medical monitor. - Female patients who are pregnant or breastfeeding. - Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 3 months following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free). - Patients seropositive for Human Immunodeficiency Virus(HIV). - Patients who are unwilling to provide informed consent. - Patients receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 30 days prior to the ASCT or planning to receive any of these treatments prior to Day +30. - Patients concurrently participating in any other clinical study involving ASCT. - Patients who are hypersensitive or intolerant to any component of the study drug formulation.

Additional Information

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
Description 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).
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by Spectrum Pharmaceuticals, Inc.