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

September 12, 2018 updated by: Parameswaran Hari, Medical College of Wisconsin

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Melphalan HCl for injection (propylene glycol free)
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)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax (Pharmacokinetics)
Time Frame: Day -2
Maximum observed plasma concentration. Derived from the individual raw data.
Day -2
AUC0-t (Pharmacokinetics)
Time Frame: Day -2
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplant-Related Mortality (TRM) Following Autologous Stem-Cell Transplantation (ASCT)
Time Frame: 100 days
TRM will be summarized descriptively (death within 100 days without relapse following ASCT).
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Investigators

  • Principal Investigator: Parameswaran Hari, MD, MRCP, MS, Medical College of Wisconsin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

June 9, 2017

Study Completion (Actual)

July 19, 2017

Study Registration Dates

First Submitted

January 24, 2016

First Submitted That Met QC Criteria

January 27, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

October 10, 2018

Last Update Submitted That Met QC Criteria

September 12, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO00026736

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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