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Doxorubicin Hydrochloride Liposome, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
Sponsored by: Oncotherapeutics
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00742404
  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
Procedure: immunologic technique
Procedure: protein analysis
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Bortezomib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients With Newly Diagnosed Multiple Myeloma (MM)

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00742404

Locations
United States, California
Comprehensive Blood and Cancer Center Recruiting
Bakersfield, California, United States, 93309-0633
Contact: Julie Leach, RN, OCN     661-862-7178        
James R. Berenson MD, Incorporated Recruiting
West Hollywood, California, United States, 90069
Contact: Regina Swift, RN     310-623-1200     jberenson@imbcr.org    
Sutter Cancer Center at Roseville Medical Center Recruiting
Roseville, California, United States, 95661
Contact: Clinical Trials Office - Sutter Cancer Center     916-454-6595        
United States, Maryland
Center for Cancer and Blood Disorders at Suburban Hospital Recruiting
Bethesda, Maryland, United States, 20817
Contact: Natalie Bongiorno     301-571-2016     nbongiorno@ccbdmd.com    
Sponsors and Collaborators
Oncotherapeutics
Investigators
Principal Investigator: James R. Berenson, MD Oncotherapeutics
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Responsible Party: Oncotherapeutics ( Clinical Research & Development Manager )
Study ID Numbers: CDR0000612434, ONCOTHER-X05272-DOXILMMY2010, DVD study
Study First Received: August 26, 2008
Last Updated: December 11, 2008
ClinicalTrials.gov Identifier: NCT00742404  
Health Authority: Unspecified

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

Study placed in the following topic categories:
Dexamethasone
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Doxorubicin
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Enzyme Inhibitors
Antibiotics, Antineoplastic
Hormones
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Autonomic Agents
Therapeutic Uses
Cardiovascular Diseases
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009