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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01660633
Recruitment Status : Completed
First Posted : August 9, 2012
Last Update Posted : April 21, 2020
Clinipace Worldwide
Beckloff Associates, Inc.
Kansas City Bioanalytical Laboratories
Information provided by (Responsible Party):
Acrotech Biopharma LLC

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) Other: Autologous Transplantation Phase 2

Detailed Description:

The sponsor of the current study is now Acrotech Biopharma, divested from Spectrum Pharmaceuticals Inc. (Spectrum), which licensed the Melphalan HC1 for Injection (Propylene Glycol-Free) product from Ligand Pharmaceuticals , formerly CyDex Pharmaceuticals, Inc. (CyDex). This new injectable form of melphalan HCL incorporates Captisol®, β cyclodextrin sulfobutyl ether sodium salts (also known as [SBE]7m-β-CD), into the product. Captisol is present to facilitate the use of an all aqueous diluent (normal saline) for reconstitution and administration of the freeze-dried product in place of the propylene glycol-ethanol diluent necessary for the currently used melphalan intravenous product. Captisol provides for solubilization and improved stability of the all aqueous reconstituted and diluted infusion solution.

This is the second of two studies supporting product registration. This study will be a multicenter study of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) conducted in 60 patients who have symptomatic MM and qualify for autologous stem cell transplantation (ASCT).

During the Study Period, patients will receive 100mg/m2 of either Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and on Day -2 for a total dose of 200mg/m2. Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints post infusion) drawn in a subset of patients on the second day of melphalan administration (Day -2).

Following one day of rest after the high dose myeloablative conditioning (Day -1), patients will receive an autologous graft (Day 0).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIb, Multicenter, Open-Label, Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free)for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation
Study Start Date : December 2012
Actual Primary Completion Date : February 2014
Actual Study Completion Date : August 2014

Arm Intervention/treatment
High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
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)
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.
Other Names:
  • Evomela
  • Alkeran

Other: Autologous Transplantation
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)
Other Name: Hematopoietic stem cell transplantation

Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day +100 ]
    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.

  2. Mucositis Severity according to World Health Organization Scoring System [ Time Frame: Until Day +30 ]
    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.

  3. Mouth Pain Scores according to a Visual Analog Scale [ Time Frame: Until Day +30 ]
    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.

  4. Treatment Related Mortality [ Time Frame: Up to Day +100 ]
    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.

Secondary Outcome Measures :
  1. MM response according to International Myeloma Working Group (IMWG) criteria. [ Time Frame: At the Day +100 visit ]
    Definition of active MM, clonal bone marrow plasma cells >10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder and one or more biomarkers of malignancy (MDEs) defined in the criteria.

  2. Myeloablation [ Time Frame: Up to Day +30 ]
    Absolute neutrophil count (ANC) <0.5 × 109/L, absolute lymphocyte count (ALC) <0.1 × 109/L, platelet count <20,000/mm3, or bleeding requiring transfusion.

  3. Neutrophil engraftment [ Time Frame: Up to Day +100 ]
    ANC >0.5 × 109/L × first 3 consecutive daily assessments

  4. Platelet engraftment [ Time Frame: Up to Day +100 ]
    Untransfused platelet measurement >20,000/mm3 × first 3 consecutive daily assessments

  5. Non-engraftment [ Time Frame: Up to Day +100 ]
    Failure to reach an ANC >0.5 × 109/L × 3 consecutive daily assessments by Day +100.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01660633

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United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kansas
University of Kansas Medical Center
Fairway, Kansas, United States, 66205
United States, Massachusetts
University of Massachusetts
Worcester, Massachusetts, United States, 01655
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Acrotech Biopharma LLC
Clinipace Worldwide
Beckloff Associates, Inc.
Kansas City Bioanalytical Laboratories
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Study Director: Tim Freeman Clinipace Worldwide
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Responsible Party: Acrotech Biopharma LLC Identifier: NCT01660633    
Other Study ID Numbers: CDX-353-002
First Posted: August 9, 2012    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020
Keywords provided by Acrotech Biopharma LLC:
Multiple Myeloma
High-Dose Melphalan
Propylene Glycol-Free
Autologous Stem Cell Transplantation
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs