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

NCT02669615 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO00026736
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; Melphalan HCl; Autologous Transplantation

Outcome Measures

Primary Outcomes (2)

• Cmax (Pharmacokinetics)

  Maximum observed plasma concentration. Derived from the individual raw data.

  Day -2

• AUC0-t (Pharmacokinetics)

  Area under the plasma concentration-time curve to the last measurable time point (AUC0-t) calculated by the trapezoidal rule. The area under the concentration-time curve (AUC) is calculated to determine the total drug exposure over a period of time.

  Day -2

Secondary Outcomes (1)

• Transplant-Related Mortality (TRM) Following Autologous Stem-Cell Transplantation (ASCT)

  100 days

Study Arms (1)

Melphalan HCl for injection (propylene glycol free)

EXPERIMENTAL

Patients will receive 200 mg/m\^2 of Melphalan HCl for injection (propylene glycol free) as a one-time infusion on day 2. Blood samples for the pharmacokinetic (PK) evaluation of melphalan will be collected after melphalan dosing (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).

Drug: Melphalan HCl for injection (propylene glycol free)

Interventions

Melphalan HCl for injection (propylene glycol free) DRUG

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.

Melphalan HCl for injection (propylene glycol free)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Injections

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Parameswaran Hari
• Organization: Medical College of Wisconsin

phari@mcw.edu

4148054600

Study Officials

• Parameswaran Hari, MD, MRCP, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 24, 2016
• First Posted: February 1, 2016
• Study Start: November 1, 2016
• Primary Completion: June 9, 2017
• Study Completion: July 19, 2017
• Last Updated: October 10, 2018
• Results First Posted: October 10, 2018

Record last verified: 2018-09

Locations

US (1)