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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Melphalan HCl for injection (propylene glycol free)

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, Melphalan HCl, Autologous Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Froedtert Hospital and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Melphalan HCl for injection (propylene glycol free)

Arm Description

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).

Outcomes

Primary Outcome Measures

Cmax (Pharmacokinetics)

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

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.

Secondary Outcome Measures

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

TRM will be summarized descriptively (death within 100 days without relapse following ASCT).

Full Information

NCT ID

NCT02669615

First Posted

January 24, 2016

Last Updated

September 12, 2018

Sponsor

Medical College of Wisconsin

1. Study Identification

Unique Protocol Identification Number

NCT02669615

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

November 1, 2016 (Actual)

Primary Completion Date

June 9, 2017 (Actual)

Study Completion Date

July 19, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical College of Wisconsin

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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: 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 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). 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

multiple myeloma, Melphalan HCl, Autologous Transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Melphalan HCl for injection (propylene glycol free)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Melphalan HCl for injection (propylene glycol free)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Cmax (Pharmacokinetics)

Description

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

Time Frame

Day -2

Title

AUC0-t (Pharmacokinetics)

Description

Time Frame

Day -2

Secondary Outcome Measure Information:

Title

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

Description

TRM will be summarized descriptively (death within 100 days without relapse following ASCT).

Time Frame

100 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Parameswaran Hari, MD, MRCP, MS

Organizational Affiliation

Medical College of Wisconsin

Official's Role

Principal Investigator

Facility Information:

Facility Name

Froedtert Hospital and the Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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