Safety & Efficacy Study High Dose Evomela Injection for MA Conditioning in MM Patients With Autologous Transplantation

NCT01660633 | Completed Phase 2 DMC

• 1 other identifier: CDX-353-002
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 6

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; High-Dose Melphalan; Propylene Glycol-Free; Autologous Stem Cell Transplantation; Captisol

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  AE coding will be performed using the MedDRA Version 11.0 or greater. The severity of the toxicities will be graded according to the NCI CTCAE Version 4.0 whenever possible. AEs occurring when treatment starts on Day -3 through Day + 100 will be recorded in the AE section of the eCRF and causality will be assigned by the Principal Investigator.

  Up to Day +100

• Mucositis Severity according to World Health Organization Scoring System

  The baseline measurement will be the last assessment prior to receiving the first dose of study treatment. The on-treatment period will be defined as the day after the first dose of study treatment to 30 days after the last dose of study treatment. The incidence of severe mucositis (WHO Grade 3 or 4) will be summarized by frequencies and percentages. In addition, the incidence of oral mucositis will be summarized by WHO grade. Time from start of the first dose of study medication to peak oral mucositis score will also be calculated.

  Until Day +30

• Mouth Pain Scores according to a Visual Analog Scale

  Baseline VAS for mouth pain and dysphagia will be the VAS score collected prior to receiving the first dose of study medication. Analyses of changes and/or percent changes from baseline in the VAS scores will be analyzed for each time point collected during the 30 day on-treatment period. The minimum and maximum VAS scores during the 30 day on-treatment period will also be calculated for mouth pain and dysphagia, and the time to the minimum and maximum VAS scores will be summarized descriptively.

  Until Day +30

• Treatment Related Mortality

  TRM, which is defined as death not due to disease progression before Day +90/+100, will be calculated. This outcome measure will be summarized by the cumulative incidence estimated with 95% confidence intervals.

  Up to Day +100

Secondary Outcomes (5)

• MM response according to International Myeloma Working Group (IMWG) criteria.

  At the Day +100 visit

• Myeloablation

  Up to Day +30

• Neutrophil engraftment

  Up to Day +100

• Platelet engraftment

  Up to Day +100

• Non-engraftment

  Up to Day +100

Study Arms (1)

High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)

OTHER

Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days).

Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free); Other: Autologous Transplantation

Interventions

High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) DRUG

200 mg melphalan/m2 will be divided into two separate, consecutive doses of 100 mg/m2 administered on day -3 and day -2 prior to ASCT. The High-Dose Melphaln HCL for Injection (Propylene Glycol-Free) will be reconstituted to 5 mg/mL (also containing 270 mg/mL of Captisol®). The Melphalan HCL for Injection (Propylene Glycol Free) will be further diluted with normal saline to a concentration of no greater than 0.45 mg/mL and infused over 30 minutes ( + or - 3 minutes)via a central venous catheter.

Also known as: Evomela, Alkeran

High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)

Autologous Transplantation OTHER

Patients who are myeloablative conditioning in multiple myeloma undergoing autologous transplantation( patients own blood-forming stem cells are collected to replace diseased bone marrow or bone marrow damaged by cancer treatment)

Also known as: Hematopoietic stem cell transplantation

High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead
• Clinipace Worldwide: collaborator
• Beckloff Associates, Inc.: collaborator
• Kansas City Bioanalytical Laboratories: collaborator

Study Sites (6)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Injections; Transplantation, Autologous; Hematopoietic Stem Cell Transplantation

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; Transplantation; Surgical Procedures, Operative; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy

Study Officials

• Tim Freeman

  Clinipace Worldwide

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 9, 2012
• Study Start: December 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2014
• Last Updated: April 21, 2020

Record last verified: 2020-04

Locations

US (6)