Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00523848
First received: August 31, 2007
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide works as first-line therapy in treating patients with previously untreated multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: thalidomide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of VDT (VELCADE, Doxil® and Thalidomide) as Frontline Therapy for Patients With Previously Untreated Multiple Myeloma (MM)

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Overall Response Rate (Complete and Partial) [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Response Rate [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Time to Disease Progression [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: June 2006
Study Completion Date: October 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Patients receive low-dose oral thalidomide once a day on days 1-28, bortezomib IV on days 1, 4, 15, and 18, and doxorubicin hydrochloride liposome IV over 60-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity
Drug: bortezomib
IV
Drug: pegylated liposomal doxorubicin hydrochloride
IV
Drug: thalidomide
Oral

Detailed Description:

OBJECTIVES:

Primary

  • To determine the overall response rate (complete response and partial response) in patients previously untreated stage I, II, or III multiple myeloma.

Secondary

  • To evaluate the complete response rate in patients treated with this regimen.
  • To determine the time to disease progression from the start of this therapy in patients treated with this regimen.

OUTLINE: Patients receive low-dose oral thalidomide once a day on days 1-28, bortezomib IV on days 1, 4, 15, and 18, and doxorubicin hydrochloride liposome IV over 60-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with residual disease who continue to show response after completion of 6 courses may receive 2 additional courses for a total of 8 courses.

After completion of study treatment, patients are followed every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of stage I, II, or III multiple myeloma requiring therapy
  • No prior systemic therapy for multiple myeloma

    • Patients who have received steroids or radiotherapy for cord compression or spinal cord disease are eligible for this study
    • Patients who have received 1 prior course of antimyeloma therapy may be enrolled at the investigator's discretion provided disease progression is not noted

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Karnofsky performance status 60-100%
  • Platelet count ≥ 75,000 cells/mm^3 (< 75,000 cells/mm^3 secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
  • ANC ≥ 1,000 cells/mm^3
  • Hemoglobin ≥ 8.0 g/dL (< 8 g/dL secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
  • Creatinine clearance > 20 mL/min
  • AST and ALT ≤ 2 times upper limit of normal (ULN) OR ≤ 3 times ULN (in the presence of liver metastases)
  • Alkaline phosphatase ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
  • Total bilirubin ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
  • Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram
  • Negative pregnancy test
  • Fertile patients must use at least 1 highly effective and 1 additional effective contraception method 4 weeks prior to, during, and 3 months after completion of study therapy
  • HIV-negative
  • Must have sufficient mental capacity to understand the explanation of the study and to provide informed consent
  • Willingness and ability to comply with the FDA-mandated S.T.E.P.S. program

Exclusion criteria:

  • Pregnant or lactating
  • Active, serious infections uncontrolled by antibiotics
  • Any medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in this clinical trial
  • History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of doxorubicin hydrochloride liposome or bortezomib, boron, or mannitol
  • Any of the following conditions:

    • History of uncontrolled New York Heart Association class II-IV heart disease or clinical evidence of congestive heart failure
    • Myocardial infarction within the past 6 months
    • Uncontrolled angina
    • Severe uncontrolled ventricular arrhythmias, ECG evidence of acute ischemia, or active conduction system abnormalities
  • Peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  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: NCT00523848

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Kelvin Lee, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00523848     History of Changes
Other Study ID Numbers: CDR0000563183, RPCI-I-59105
Study First Received: August 31, 2007
Results First Received: July 12, 2013
Last Updated: July 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Bortezomib
Thalidomide
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on July 28, 2014