Alternative Schedule of Velcade/Dexamethasone Plus Doxil for Patients With Multiple Myeloma

A Phase II, Open Label Study Evaluating an Alternative Schedule of Velcade/Dexamethasone Plus Doxil in the Treatment of Multiple Myeloma

The current study is being conducted to evaluate the possibility that a different schedule of bortezomib, doxorubicin HCl liposome, and dexamethasone might decrease the incidence of peripheral neuropathy yet maintain similar efficacy and allow maintenance of bortezomib dosing for a longer period.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: bortezomib; Drug: dexamethasone; Drug: doxorubicin HCl liposome

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Verne, California, United States, 91750
      • Wilshire Oncology Medical Group, Inc.
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Medical Oncology & Hematology
  • Florida
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
  • Georgia
    • Athens, Georgia, United States, 30607
      • Northeast Georgia Cancer Care
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates, PC
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, PC
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Cancer Center
  • Maryland
    • Clinton, Maryland, United States, 20735
      • Oncology-Hematology Associates, P.A.
  • Montana
    • Billings, Montana, United States, 59101
      • Hematology Oncology Centers of the Northern Rockies, PC
  • New York
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates
  • Ohio
    • Canton, Ohio, United States, 44718
      • Tri-County Hematology and Oncology Associates
    • Columbus, Ohio, United States, 43215
      • Mid Ohio Oncology/Hematology, Inc.
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17605
      • Lancaster Cancer Center, Ltd.
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Cancer Specialists of Tidewater, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is at least 18 years of age.
• Patient has confirmed diagnosis of relapsed/refractory multiple myeloma with measurable disease by serum or urine. Measurable disease defined as monoclonal protein of ≥ 1g/dl on serum protein electrophoresis (SPEP) or > 200 mg urine M protein/ 24 hours
• Patient has received at least 1 prior treatment regimen. (Prior treatment with bortezomib is allowed.)
• Patient has ECOG ≤ 2
• Patient provides voluntary written informed consent before performance of any study-relates procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Patients who have received prior high dose chemotherapy with stem cell support are eligible for this study.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

• Patient has a platelet count of < 50, 000 cells/mm³, within 14 days before enrollment.
• Patient has an absolute neutrophil count (ANC) ≤ 750/mm³ within 14 days before enrollment.
• Patient has a calculated or measured creatinine clearance of < 20 mL/min within 14 days before enrollment and/or serum creatinine ≥ 2.5 mg/dl.
• Patient has hemoglobin < 7.5 g/dl.
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
• Patient has received a total cumulative dosage of anthracyclines exceeding 550 mg/m2.
• Patient has hypersensitivity to boron or mannitol.
• Patient has history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of DOXIL.
• Patient has clinically significant coexisting illness unrelated to myeloma.
• Patient has uncontrolled diabetes.
• Patient has plasma cell leukemia.
• Patient has serum bilirubin > 1.5 x upper normal limit, alanine aminotransaminase (ALT), aspartate aminotransferase (AST) > 2.5 x upper normal limit (ULN), or alkaline phosphatase > 2.5 x ULN.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG)pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs within 14 days before enrollment.
• Patient has serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-emergent Peripheral Neuropathy	Every 4 weeks from start of treatment until end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP)		TTP was measured from day 1 of treatment until time of progression, assessed up to 40 months
Number of Participants With Treatment Response	Complete Response (CR), Partial Response (PR), and Minor Response (MR) each required stable bone disease and normal calcium levels. CR also required 100% serum protein electrophoresis (SPEP) reduction, negative immunofixation (IF), 100% urine protein electrophoresis (UPEP)reduction, and <5% plasma cells in bone marrow. PR also required >=50% SPEP reduction, >=90% UPEP reduction, and >=50% reduction in plasma cells in bone marrow. MR also required >=25% SPEP reduction, >=50% UPEP reduction, and > 25% reduction in plasma cells.	Every 8 weeks from start of treatment until end of treatment
Relative Dose Intensity of Bortezomib	Relative dose intensity is defined as actual dose/scheduled dose. Bortezomib is administered on Days 1, 4, 15, and 18 every 28 days.	Each dose of bortezomib (days 1, 4, 15, and 18 every 28 days)

Collaborators and Investigators

• Sponsor: Accelerated Community Oncology Research Network
• Collaborators: Millennium Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Johnetta Blakely, MD, Accelerared Community Oncology Research Network, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 16, 2006
• First Submitted That Met QC Criteria: August 17, 2006
• First Posted (Estimate): August 18, 2006

Study Record Updates

• Last Update Posted (Estimate): April 6, 2012
• Last Update Submitted That Met QC Criteria: April 4, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Refractory Multiple Myeloma; Relapsed Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Dexamethasone; Bortezomib; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: ACORN ALJBMM0502