Clinical trial NCT01660633: Safety & Efficacy Study High Dose Evomela Injection for MA Conditioning in MM Patients With Autologous Transplantation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
High-Dose Melphalan
Propylene Glycol-Free
Autologous Stem Cell Transplantation
Captisol
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Clinipace Worldwide
name: Beckloff Associates, Inc.
name: Kansas City Bioanalytical Laboratories
First posted: 2012-08-09
Enrollment: 61
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The sponsor of the current study is now Acrotech Biopharma, divested from Spectrum Pharmaceuticals Inc. (Spectrum), which licensed the Melphalan HC1 for Injection (Propylene Glycol-Free) product from Ligand Pharmaceuticals , formerly CyDex Pharmaceuticals, Inc. (CyDex). 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to Day +100
measure: Mucositis Severity according to World Health Organization Scoring System
timeFrame: Until Day +30
measure: Mouth Pain Scores according to a Visual Analog Scale
timeFrame: Until Day +30
measure: Treatment Related Mortality
timeFrame: Up to Day +100
Secondary outcomes:
measure: MM response according to International Myeloma Working Group (IMWG) criteria.
timeFrame: At the Day +100 visit
measure: Myeloablation
timeFrame: Up to Day +30
measure: Neutrophil engraftment
timeFrame: Up to Day +100
measure: Platelet engraftment
timeFrame: Up to Day +100
measure: Non-engraftment
timeFrame: Up to Day +100
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Clinipace Worldwide
name: Tim Freeman
role: STUDY_DIRECTOR
References: