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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

Phase 2/Phase 3
70 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

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

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

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will be withdrawn through an indwelling i.v. cannula on the first day of administration of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

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

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Up to Day +100

Safety Issue:


Principal Investigator

Tim Freeman

Investigator Role:

Study Director

Investigator Affiliation:

Clinipace Worldwide


United States: Food and Drug Administration

Study ID:




Start Date:

December 2012

Completion Date:

March 2014

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • High-Dose Melphalan
  • Propylene Glycol-Free
  • Autologous Stem Cell Transplantation
  • Captisol
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Washington University School of Medicine Saint Louis, Missouri  63110
University of Kansas Medical Center Kansas City, Kansas  66160-7353
University of Massachusetts Worcester, Massachusetts  01655
Medical College of Wisconsin/Froedtert Hospital Milwaukee, Wisconsin  53226