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

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
dexamethasone
pegylated liposomal doxorubicin hydrochloride
protein analysis
immunologic technique
Sponsored by
Oncotherapeutics
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Clinical Research Center, Incorporated
  • Comprehensive Blood and Cancer Center
  • San Diego Pacific Oncology and Hematology Associates, Incorporated - Escondido
  • Loma Linda University Cancer Institute at Loma Linda University Medical Center
  • Oncology Care Medical Associates - San Gabriel
  • Desert Cancer Care
  • Sutter Cancer Center at Roseville Medical Center
  • Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara
  • James R. Berenson MD, Incorporated
  • Center for Cancer and Blood Disorders
  • New York Medical College
  • Charleston Hematology Oncology Associates, PA

Outcomes

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

Secondary Outcome Measures

Safety and tolerability as assessed by NCI CTCAE v3.0
Time to progression
Time to response
Duration of response
Progression-free survival
Overall survival
Changes in serum M-protein
Changes in 24-hour urine M-protein

Full Information

First Posted
August 26, 2008
Last Updated
December 17, 2013
Sponsor
Oncotherapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00742404
Brief Title
Doxorubicin Hydrochloride Liposome, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
Official Title
A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients With Newly Diagnosed Multiple Myeloma (MM)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Unknown status
Study Start Date
July 2008 (undefined)
Primary Completion Date
July 2010 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Oncotherapeutics

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
pegylated liposomal doxorubicin hydrochloride
Intervention Type
Genetic
Intervention Name(s)
protein analysis
Intervention Type
Other
Intervention Name(s)
immunologic technique
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Safety and tolerability as assessed by NCI CTCAE v3.0
Title
Time to progression
Title
Time to response
Title
Duration of response
Title
Progression-free survival
Title
Overall survival
Title
Changes in serum M-protein
Title
Changes in 24-hour urine M-protein

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James R. Berenson, MD
Organizational Affiliation
Oncotherapeutics
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arizona Clinical Research Center, Incorporated
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
Comprehensive Blood and Cancer Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309-0633
Country
United States
Facility Name
San Diego Pacific Oncology and Hematology Associates, Incorporated - Escondido
City
Escondido
State/Province
California
ZIP/Postal Code
92025
Country
United States
Facility Name
Loma Linda University Cancer Institute at Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Oncology Care Medical Associates - San Gabriel
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
Desert Cancer Care
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
Sutter Cancer Center at Roseville Medical Center
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
James R. Berenson MD, Incorporated
City
West Hollywood
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Charleston Hematology Oncology Associates, PA
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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