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A Pharmacokinetic Study of Melphalan HCL for Injection (Propylene Glycol-Free) and Alkeran for Injection for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00925782
First received: June 18, 2009
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

To assess and compare the pharmacokinetics of Melphalan HCL for Injection (Propylene Glycol-Free) versus Alkeran for Injection in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT).


Condition Intervention Phase
Multiple Myeloma
Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection
Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIA Open-Label, Randomized, Pharmacokinetic Comparative, Cross-Over Study of Melphalan HCL for Injection (Propylene Glycol-Free) and Alkeran for Injection 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:
  • Area Under the Curve (0-t) [ Time Frame: Day -3 and Day -2 ] [ Designated as safety issue: No ]

    AUC (0-t) was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations.

    The AUC results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.


  • Concentration-Max (Cmax) [ Time Frame: Day -3 and Day -2 ] [ Designated as safety issue: No ]

    Cmax was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations.

    The Cmax results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.



Secondary Outcome Measures:
  • Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    ANC <0.5 × 109/L, absolute lymphocyte count (ALC) <0.1 × 109/L, platelet count <20,000/mm3, or bleeding requiring transfusion. The first of 2 consecutive days for which cell counts drop below these cutoff levels was recorded as the date of myeloablation.

    Since the two treatments were administered consecutively with 1 day rest, the time to myeloablation and myeloablation rate was measured after both treatments were administered.

    Comparison of sequence effect was not planned in the study and due to small sample size, it was not performed.


  • Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    Neutrophil engraftment was defined as the first day of 3 consecutive days where ANC (absolute neutrophil count) was higher than 500/ul. The two drug treatments in this cross-over design were administered on 2 subsequent days (Day -3 and Day -2). No per arm analysis was performed.

    Since the two treatments were administered consecutively with 1 day rest, the time to engraftment and engraftment rate was measured after both treatments were administered.



Enrollment: 24
Study Start Date: January 2010
Study Completion Date: July 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Melphalan-Alkeran
Subjects begin with treatment Melphalan and crossover to treatment Alkeran
Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection
Patients will be randomized to receive 100 mg/m2 of Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and Alkeran for Injection on Day -2 prior to ASCT.
Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Patients will be randomized to receive 100 mg/m2 of Alkeran for Injection on Day -3 and Melphalan HCL for Injection (Propylene Glycol-Free)on Day -2 prior to ASCT.
Alkeran-Melphalan
Subjects begin with treatment Alkeran and crossover to treatment Melphalan.
Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection
Patients will be randomized to receive 100 mg/m2 of Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and Alkeran for Injection on Day -2 prior to ASCT.
Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Patients will be randomized to receive 100 mg/m2 of Alkeran for Injection on Day -3 and Melphalan HCL for Injection (Propylene Glycol-Free)on Day -2 prior to ASCT.

Detailed Description:

This study will be a multicenter, open-label, randomized, comparative, cross-over study of high-dose Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection conducted in 24 patients who have symptomatic MM and qualify for ASCT.

During the Study Period, patients will be randomized to receive 100mg/m2 of either Melphalan HCl for Injection (Propylene Glycol-Free) or Alkeran for Injection on Day -3 and the alternate drug product on Day -2. Blood samples for pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula each day of melphalan dosing (Day -3 and Day -2).

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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with symptomatic MM requiring treatment at diagnosis or anytime thereafter.
  • Patients with MM who qualify for ASCT therapy who have received appropriate primary induction therapy for transplantation.
  • Adult patients (≥ 18 years old) who are 70 years of age or younger at time of transplant; patients greater than 70 years of age may qualify 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 which is defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based upon patient weight.
  • Patients with adequate organ function as measured by:

    • Cardiac: Left ventricular ejection fraction at rest >40% (documented within 12 weeks prior to Day -3).
    • Hepatic: Bilirubin <2 × the upper limit of normal (ULN) and ALT/AST <3 × ULN.
    • Renal: Creatinine clearance >40 mL/minutes (measured or calculated/estimated).
    • Pulmonary: DLCO, FEV1, FVC >50% of predicted value (corrected for Hgb) or O2 saturation > 92% on room air (documented within 12 weeks prior to Day -3)

Exclusion Criteria:

  • Patients who have never advanced beyond Stage 1 MM since diagnosis.
  • Patients who have previously received more than one autologous stem cell transplant.
  • Patients with plasma cell leukemia.
  • Patients with MM and systemic AL amyloidosis.
  • ECOG performance status ≥2.
  • Patients with uncontrolled hypertension.
  • Patients with an 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 ß-HCG) or breastfeeding.
  • Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 1 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 21 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.
  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: NCT00925782

Locations
United States, Kansas
University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Omar Aljitawi, MD University of Kansas
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00925782     History of Changes
Other Study ID Numbers: CDX-353-001
Study First Received: June 18, 2009
Results First Received: May 8, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
autologous stem cell transplantation

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

ClinicalTrials.gov processed this record on November 24, 2014