Pharmacokinetic Study of Propylene Glycol-Free Melphalan HCl for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation

A Phase II, Open-Label, Pharmacokinetic Study of Propylene Glycol-Free Melphalan HCl for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation

This study is a single-center, open-label study of high-dose Melphalan HCl (hydrochloric acid) for injection (propylene glycol-free Melphalan) conducted in 24 patients, who have symptomatic multiple myeloma and qualify for autologous stem-cell transplantation (ASCT).

There will be three distinct evaluation periods in this trial: a pretreatment period, a study period and a follow-up period.

OVERVIEW: This study is a single-center, open-label study of high-dose Melphalan HCl for injection (propylene glycol free Melphalan) conducted in 24 patients, who have symptomatic multiple myeloma and qualify for ASCT.

There will be three distinct evaluation periods in this trial: a pretreatment period, a study period and a follow-up period.

PRETREATMENT:

Pretreatment Period Evaluations (Days -30 to -3). Baseline assessments will be collected within 30 days of dosing with Melphalan HCl for injection (propylene glycol free), after the patient has signed the informed consent. These include clinical and laboratory assessments (e.g., medical history and physical examination, hematology, urine analysis, creatinine clearance), chest X-ray and vital signs.

STUDY TREATMENT:

1. During the study period, patients will receive 200 mg/m^2 of Melphalan HCl for injection (propylene glycol free) as a one-time infusion on day
2. Following one day of rest after the myeloablative Melphalan conditioning (day -1), patients will receive an autologous graft with a minimum cell dose of 2 × 106 CD34+ cells/kg of patient body weight (day 0).
3. Pharmacokinetic, efficacy and safety evaluations will be performed during the study period.

FOLLOW-UP:

ASCT Day +1 until Day+100. During the follow-up period, patients will return for daily laboratory tests (hematology and basic serum chemistry) and will be evaluated weekly by their physicians until the engraftment date, with the final end-of-study evaluation occurring up to seven days after engraftment date. During the follow-up period, the tests (e.g., physical examination, CBC, vital signs, full serum chemistry panel, bone marrow biopsy) will be performed weekly until engraftment (unless otherwise specified).

Inclusion Criteria:

• Patients with symptomatic multiple myeloma (MM) requiring treatment at or following diagnosis.
• Patients with MM, who qualify for ASCT therapy, and have received pretransplant therapy prior to transplantation.
• Adult patients (≥18 years of age) meeting local institutional criteria to receive a total Melphalan dose of 200 mg/m^2 as a conditioning regimen.
• Patients with an adequate autologous graft, which is defined as an unmanipulated, cryopreserved, peripheral blood cell graft containing at least 2 × 106 CD34+ cells/kg, based on patient weight.
• Patients with adequate organ function, as measured by:
• Cardiac: Left ventricular ejection fraction at rest >40% (documented within 30 days prior to Day -3).
• Hepatic: Bilirubin <2 × the upper limit of normal (ULN) and Alanine transaminase/Aspartate transaminase (ALT/AST) <3 × ULN.
• Renal: Creatinine clearance >40 mL/min (measured or calculated/estimated).
• Pulmonary: Adjusted Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) >50% of predicted value (corrected for hemoglobin level [Hgb]) and documented within prior to day -3.

Exclusion Criteria:

• Patients with systemic AL amyloidosis (immunoglobulin light chain amyloidosis).
• Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
• Patients with uncontrolled hypertension.
• Patients with a serious active bacterial, viral or fungal infection.
• 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 (positive human chorionic gonadotropin [ß-HCG]) or breastfeeding.
• Female patients of childbearing potential, who are unwilling to use adequate contraceptive techniques during and for one month following study treatment with Melphalan HCl for injection (propylene glycol free).
• Patients seropositive for 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 study discharge.
• Patients concurrently participating in any other clinical study.
• Patients who are hypersensitive or intolerant to any component of the study drug formulation.