Doxorubicin Hydrochloride Liposome, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00742404
First received: August 26, 2008
Last updated: December 17, 2013
Last verified: June 2010
  Purpose

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

PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride liposome together with bortezomib and dexamethasone works in treating patients with newly diagnosed multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: dexamethasone
Drug: pegylated liposomal doxorubicin hydrochloride
Genetic: protein analysis
Other: immunologic technique
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients With Newly Diagnosed Multiple Myeloma (MM)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete response, very good partial response, partial response, and minimal response) as assessed by modified Bladé criteria at baseline, on day 1 of each course, and at end-of-study [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Time to progression [ Designated as safety issue: No ]
  • Time to response [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Changes in serum M-protein [ Designated as safety issue: No ]
  • Changes in 24-hour urine M-protein [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: July 2008
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the response rate (i.e., complete response, very good partial response , partial response, and minimal response) in patients with newly diagnosed multiple myeloma treated with pegylated liposomal doxorubicin hydrochloride, bortezomib, and dexamethasone.

Secondary

  • To assess the safety and tolerability of this regimen in these patients.
  • To determine the time to disease progression, time to response, duration of response, progression-free survival, and overall survival of patients treated with this regimen.

OUTLINE: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 30-90 minutes, dexamethasone IV, and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected at baseline and periodically during study for M-protein analysis by electrophoresis and immunofixation.

After completion of study therapy, patients are followed periodically.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma based on the following criteria:

    • Major criteria

      • Plasmacytomas on tissue biopsy (1)
      • Bone marrow plasmacytosis (> 30% plasma cells) (2)
      • Monoclonal immunoglobulin spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL and kappa or lambda light chain excretion > 1 g/day on 24-hour urine protein electrophoresis (3)
    • Minor criteria

      • Bone marrow plasmacytosis (10% to 30% plasma cells) (a)
      • Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b)
      • Lytic bone lesions (c)
      • Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL (d)
  • Meets 1 of the following sets of diagnostic criteria:

    • Any two of the major criteria
    • Major criteria 1 and minor criteria b, c, and d
    • Major criteria 3 and minor criteria a or c
    • Minor criteria a, b, c, OR a, b, d
  • Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/24 hours, or evidence of lytic bone disease

    • No nonmeasurable disease (i.e., non-secretory or oligosecretory multiple myeloma)
  • Symptomatic, newly diagnosed, and previously untreated multiple myeloma
  • No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
  • No plasma cell leukemia

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 3 months
  • ANC ≥ 1,500/mm^³ (≥ 1,000/mm^³ if bone marrow is extensively infiltrated)
  • Platelet count ≥ 75,000/mm^³ (≥ 50,000/mm^³ if bone marrow is extensively infiltrated)
  • Hemoglobin ≥ 8.0 g/dL
  • AST and ALT ≤ 3.0 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 2.0 times ULN
  • Creatinine clearance ≥ 30 mL/min OR creatinine > 10 mL/min and < 30 mL/min for patients with significant myelomatous involvement of the kidneys
  • Serum potassium ≥ lower limit of normal (LLN)
  • Serum sodium ≥ LLN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No peripheral neuropathy ≥ grade 2 within past 14 days
  • No impaired cardiac function or clinically significant cardiac disease, including any one of the following:

    • Myocardial infarction within the past 6 months
    • New York Heart Association class II-IV heart failure
    • Uncontrolled angina
    • Clinically significant pericardial disease
    • Severe uncontrolled ventricular arrhythmias
    • LVEF below normal by ECHO or MUGA scan
    • ECG evidence of acute ischemia or active conduction system abnormalities

      • Screening ECG abnormality must be documented by the investigator as not medically relevant
  • No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L])
  • No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could preclude study treatment
  • No known HIV positivity or hepatitis B or C positivity

    • Baseline testing for HIV and hepatitis B or C is not required
  • No history of allergic reaction attributable to compounds of similar chemical or biological composition to doxorubicin, bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior or concurrent anti-myeloma therapy except steroids

    • Prior prednisone for ≤ 4 days at a total of 400 mg (or an equivalent potency of another steroid) allowed
    • No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent) other than dexamethasone
  • More than 4 weeks since prior major surgery and recovered

    • Prior kyphoplasty with oncotherapeutic drugs allowed at the investigator's discretion
  • More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy
  • More than 14 days since other prior and no other concurrent investigational drugs
  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: NCT00742404

Locations
United States, Arizona
Arizona Clinical Research Center, Incorporated
Tucson, Arizona, United States, 85712
United States, California
Comprehensive Blood and Cancer Center
Bakersfield, California, United States, 93309-0633
San Diego Pacific Oncology and Hematology Associates, Incorporated - Escondido
Escondido, California, United States, 92025
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Oncology Care Medical Associates - San Gabriel
Los Angeles, California, United States, 90057
Desert Cancer Care
Rancho Mirage, California, United States, 92270
Sutter Cancer Center at Roseville Medical Center
Roseville, California, United States, 95661
Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara
Santa Barbara, California, United States, 93105
James R. Berenson MD, Incorporated
West Hollywood, California, United States, 90069
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, South Carolina
Charleston Hematology Oncology Associates, PA
Charleston, South Carolina, United States, 29403
Sponsors and Collaborators
Oncotherapeutics
Investigators
Principal Investigator: James R. Berenson, MD Oncotherapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: Regulatory Affairs Associate, Oncotherapeutics
ClinicalTrials.gov Identifier: NCT00742404     History of Changes
Other Study ID Numbers: CDR0000612434, ONCOTHER-X05272-DOXILMMY2010, DVD study
Study First Received: August 26, 2008
Last Updated: December 17, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
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
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Liposomal doxorubicin
Bortezomib
Doxorubicin
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014