Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Clinipace LTD
Kansas City Bioanalytical Laboratories
Beckloff Associates, Inc.
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01660633
First received: August 2, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day +100 ] [ Designated as safety issue: Yes ]
  • Mucositis Severity according to World Health Organization Scoring System [ Time Frame: Until Day +30 ] [ Designated as safety issue: Yes ]
  • Mouth Pain Scores according to a Visual Analog Scale [ Time Frame: Until Day +30 ] [ Designated as safety issue: Yes ]
  • Treatment Related Mortality [ Time Frame: Up to Day +100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • MM response according to International Myeloma Working Group (IMWG) criteria. [ Time Frame: At the Day +100 visit ] [ Designated as safety issue: No ]
  • Myeloablation [ Time Frame: Up to Day +30 ] [ Designated as safety issue: No ]
    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.

  • Neutrophil engraftment [ Time Frame: Up to Day +100 ] [ Designated as safety issue: No ]
    ANC >0.5 × 109/L × first 3 consecutive daily assessments

  • Platelet engraftment [ Time Frame: Up to Day +100 ] [ Designated as safety issue: No ]
    Untransfused platelet measurement >20,000/mm3 × first 3 consecutive daily assessments

  • Non-engraftment [ Time Frame: Up to Day +100 ] [ Designated as safety issue: No ]
    Failure to reach an ANC >0.5 × 109/L × 3 consecutive daily assessments by Day +100.


Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Study Completion Date: August 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

The sponsor of the current study, Ligand Pharmaceuticals Inc. (Ligand), previously CyDex Pharmaceuticals, Inc. (CyDex), is developing Melphalan HCL for Injection (Propylene Glycol-Free) as an orphan drug product for use as a high dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation. 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).

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01660633

Locations
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
St 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
Spectrum Pharmaceuticals, Inc
Clinipace LTD
Kansas City Bioanalytical Laboratories
Beckloff Associates, Inc.
Investigators
Study Director: Tim Freeman Clinipace Worldwide
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01660633     History of Changes
Other Study ID Numbers: CDX-353-002
Study First Received: August 2, 2012
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Multiple Myeloma
High-Dose Melphalan
Propylene Glycol-Free
Autologous Stem Cell Transplantation
Captisol

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014