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Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma

Primary Purpose

DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Laboratory Biomarker Analysis
Pegylated Liposomal Doxorubicin Hydrochloride
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for DS Stage I Plasma Cell Myeloma

Eligibility Criteria

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

Inclusion Criteria: Patients must have a histologically confirmed diagnosis of symptomatic multiple myeloma with evaluable disease parameters A diagnosis of symptomatic multiple myeloma requires: A monoclonal serum and/or urine protein Clonal bone marrow plasmacytosis, or a histologically confirmed plasmacytoma Related organ or tissue impairment, consisting of: Hypercalcemia (serum calcium > 0.25 mmol/l above the upper limit of normal, or > 2.75 mmol/l [i.e. > 11.5 mg/dl]) AND/OR Renal insufficiency (serum creatinine > 173 mmol/l [i.e., > 2 mg/dL]); (please note that serum creatinine may not be >= 2.5 mg/dL) AND/OR Anemia (hemoglobin 2 g/dl below the lower limit of normal, or hemoglobin < 10 g/dl) AND/OR Bony lesions (lytic bony lesions, or osteoporosis with compression fractures) AND/OR Other findings, such as symptomatic hyperviscosity, amyloidosis, or recurring bacterial infections (> 2 episodes in 12 months) Patients may not have undergone any prior therapy, with the following exceptions: Prior plasmapheresis with plasma exchange (PLEX) for a hyperviscosity syndrome is allowed, providing the patient has no current evidence of hyperviscosity and has not required PLEX for at least one week prior to initiation of therapy Prior radiation therapy to areas of spinal cord compression by plasmacytomas, painful lesions due to bony involvement, or other myeloma-related indications, is allowed provided that radiation will have been completed 3 weeks before initiation of therapy Prior surgical intervention, such as for bony fractures or other myeloma-related complications, is allowed provided that this will have been completed 3 weeks before the initiation of therapy, and patients have recovered from surgery Prior therapy with corticosteroids for indications other than multiple myeloma is allowed, provided such therapy has been discontinued at least two weeks prior to study entry, and at least two weeks before their baseline disease evaluation Prior supportive therapy with bisphosphonates or erythropoietin is allowed Inclusion of females of childbearing potential requires a negative pregnancy test Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Patients may not have a prior history of a hypersensitivity reaction to pegylated liposomal doxorubicin or doxorubicin, bortezomib or other boronic acid-based compounds Patients with a history of reactions to liposomal drug formulations other than pegylated liposomal doxorubicin will be evaluated individually, and if their reactions were felt to have been due to the liposomal component itself, as opposed to the encapsulated agent, they will be excluded at the discretion of the investigators Patients who are known to be human immunodeficiency virus (HIV)-seropositive and are taking anti-retrovirals may not participate in this study; patients who are HIV-seropositive and not on anti-retroviral therapy, and who otherwise meet the organ function criteria, will be eligible for the study Patients who are known to have active hepatitis A, B, or C viral infection may not participate in this study No electrocardiogram (EKG) evidence of acute ischemia No EKG evidence of medically significant conduction system abnormalities No history of myocardial infarction within the last 6 months Left ventricular ejection fraction (LVEF) must be >= 45% by either echocardiography or radionuclide-based multiple gated acquisition (radionuclide ventriculography [RNV] or multiple gate acquisition scan [MUGA]) No class 3 or class 4 New York Heart Association congestive heart failure Creatinine < 2.5 mg/dL Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times the upper limit of the institutional normal value Total bilirubin =< 1.2 times the upper limit of the institutional normal value Absolute neutrophil count (ANC) >= 1,000/ul Platelets >= 100,000/ul Hemoglobin >= 8 g/dl (transfusion- and/or growth factor-dependent patients are not excluded if the above parameters can be achieved with such support) For those patients receiving warfarin (Coumadin), unfractionated heparin, or low-molecular weight heparin therapy, the applicable coagulation parameter that is being monitored must be within the accepted therapeutic ranges for those indications

Sites / Locations

  • Palo Alto Medical Foundation-Camino Division
  • Christiana Care Health System-Christiana Hospital
  • MedStar Georgetown University Hospital
  • MedStar Washington Hospital Center
  • Holy Cross Hospital
  • Jupiter Medical Center
  • Mount Sinai Medical Center
  • AdventHealth Orlando
  • University of Chicago Comprehensive Cancer Center
  • Kansas City NCI Community Oncology Research Program
  • Walter Reed National Military Medical Center
  • Minneapolis VA Medical Center
  • Washington University School of Medicine
  • Missouri Baptist Medical Center
  • Center for Cancer Care and Research
  • Frisbie Hospital
  • Roswell Park Cancer Institute
  • UNC Lineberger Comprehensive Cancer Center
  • Novant Health Presbyterian Medical Center
  • Lenoir Memorial Hospital
  • Wake Forest University Health Sciences
  • Greenville Health System Cancer Institute-Eastside
  • Central Vermont Medical Center/National Life Cancer Treatment
  • University of Vermont and State Agricultural College
  • Danville Regional Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bortezomib and pegylated liposomal doxorubicin)

Arm Description

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 4. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

CR+nCR rate
Will be estimated with an exact 90% confidence interval.

Secondary Outcome Measures

CR+nCR+PR rate
Will be estimated with an exact 90% confidence interval.
Maximal response rate
Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Toxicities will be tabulated by type and grade.
Progression-free survival
Will be estimated using the Kaplan-Meier method.
Overall survival
Will be estimated using the Kaplan-Meier method.
Changes in IL-6 and MIP-1
The association of response with pre-treatment characteristics such as cytogenetics and fluorescence in situ hybridization and with early changes in IL-6 and MIP-1 will be described by reporting response rates (and their confidence intervals) according to subgroup (e.g., response rates by age group; response rates by large/small change in IL-6 level).

Full Information

First Posted
August 4, 2004
Last Updated
September 20, 2019
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00088855
Brief Title
Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma
Official Title
Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
June 15, 2004 (Actual)
Primary Completion Date
October 31, 2006 (Actual)
Study Completion Date
January 8, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial studies the side effects and how well bortezomib and pegylated liposomal doxorubicin hydrochloride work in treating patients multiple myeloma that are experiencing symptoms and have not received prior treatment. Bortezomib and pegylated liposomal doxorubicin hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the complete response (CR) + near-complete response (nCR) rate of the bortezomib/pegylated liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) regimen in patients with previously untreated, symptomatic multiple myeloma. II. To evaluate the toxicity of the bortezomib/pegylated liposomal doxorubicin regimen in patients with previously untreated, symptomatic multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the overall response rate, including patients with CR, nCR, and partial response (PR), of the bortezomib/pegylated liposomal doxorubicin regimen in patients with previously untreated, symptomatic multiple myeloma. II. To evaluate the impact of therapy with the bortezomib/pegylated liposomal doxorubicin regimen on the ability to collect peripheral blood stem cells in those patients going on to subsequent autologous stem cell transplantation. III. To evaluate the time to progression (TTP) in all patients receiving bortezomib/pegylated liposomal doxorubicin therapy, both those who go on to autologous stem cell transplantation and those who do not go on to transplantation. IV. To evaluate the value of early changes in levels of serum interleukin 6 (IL-6) and macrophage inflammatory protein 1 alpha (MIP-1α) as predictors of response to bortezomib/pegylated liposomal doxorubicin. V. To correlate pre-treatment clinical and biological characteristics with response to therapy and toxicity. OUTLINE: Patients receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11 and pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 4. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 weeks for 2 years and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bortezomib and pegylated liposomal doxorubicin)
Arm Type
Experimental
Arm Description
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 4. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin Hydrochloride
Other Intervention Name(s)
ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, doxorubicin hydrochloride liposome, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
CR+nCR rate
Description
Will be estimated with an exact 90% confidence interval.
Time Frame
After 18 weeks (6 courses of treatment)
Secondary Outcome Measure Information:
Title
CR+nCR+PR rate
Description
Will be estimated with an exact 90% confidence interval.
Time Frame
After 18 weeks (6 courses of treatment)
Title
Maximal response rate
Time Frame
After 18 weeks (6 courses of treatment)
Title
Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Description
Toxicities will be tabulated by type and grade.
Time Frame
Up to 5 years
Title
Progression-free survival
Description
Will be estimated using the Kaplan-Meier method.
Time Frame
From on-study date to the date of progression or death, whichever comes first, assessed up to 5 years
Title
Overall survival
Description
Will be estimated using the Kaplan-Meier method.
Time Frame
From on-study date to the date of death, assessed up to 5 years
Title
Changes in IL-6 and MIP-1
Description
The association of response with pre-treatment characteristics such as cytogenetics and fluorescence in situ hybridization and with early changes in IL-6 and MIP-1 will be described by reporting response rates (and their confidence intervals) according to subgroup (e.g., response rates by age group; response rates by large/small change in IL-6 level).
Time Frame
Baseline to up to day 2 of course 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a histologically confirmed diagnosis of symptomatic multiple myeloma with evaluable disease parameters A diagnosis of symptomatic multiple myeloma requires: A monoclonal serum and/or urine protein Clonal bone marrow plasmacytosis, or a histologically confirmed plasmacytoma Related organ or tissue impairment, consisting of: Hypercalcemia (serum calcium > 0.25 mmol/l above the upper limit of normal, or > 2.75 mmol/l [i.e. > 11.5 mg/dl]) AND/OR Renal insufficiency (serum creatinine > 173 mmol/l [i.e., > 2 mg/dL]); (please note that serum creatinine may not be >= 2.5 mg/dL) AND/OR Anemia (hemoglobin 2 g/dl below the lower limit of normal, or hemoglobin < 10 g/dl) AND/OR Bony lesions (lytic bony lesions, or osteoporosis with compression fractures) AND/OR Other findings, such as symptomatic hyperviscosity, amyloidosis, or recurring bacterial infections (> 2 episodes in 12 months) Patients may not have undergone any prior therapy, with the following exceptions: Prior plasmapheresis with plasma exchange (PLEX) for a hyperviscosity syndrome is allowed, providing the patient has no current evidence of hyperviscosity and has not required PLEX for at least one week prior to initiation of therapy Prior radiation therapy to areas of spinal cord compression by plasmacytomas, painful lesions due to bony involvement, or other myeloma-related indications, is allowed provided that radiation will have been completed 3 weeks before initiation of therapy Prior surgical intervention, such as for bony fractures or other myeloma-related complications, is allowed provided that this will have been completed 3 weeks before the initiation of therapy, and patients have recovered from surgery Prior therapy with corticosteroids for indications other than multiple myeloma is allowed, provided such therapy has been discontinued at least two weeks prior to study entry, and at least two weeks before their baseline disease evaluation Prior supportive therapy with bisphosphonates or erythropoietin is allowed Inclusion of females of childbearing potential requires a negative pregnancy test Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Patients may not have a prior history of a hypersensitivity reaction to pegylated liposomal doxorubicin or doxorubicin, bortezomib or other boronic acid-based compounds Patients with a history of reactions to liposomal drug formulations other than pegylated liposomal doxorubicin will be evaluated individually, and if their reactions were felt to have been due to the liposomal component itself, as opposed to the encapsulated agent, they will be excluded at the discretion of the investigators Patients who are known to be human immunodeficiency virus (HIV)-seropositive and are taking anti-retrovirals may not participate in this study; patients who are HIV-seropositive and not on anti-retroviral therapy, and who otherwise meet the organ function criteria, will be eligible for the study Patients who are known to have active hepatitis A, B, or C viral infection may not participate in this study No electrocardiogram (EKG) evidence of acute ischemia No EKG evidence of medically significant conduction system abnormalities No history of myocardial infarction within the last 6 months Left ventricular ejection fraction (LVEF) must be >= 45% by either echocardiography or radionuclide-based multiple gated acquisition (radionuclide ventriculography [RNV] or multiple gate acquisition scan [MUGA]) No class 3 or class 4 New York Heart Association congestive heart failure Creatinine < 2.5 mg/dL Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times the upper limit of the institutional normal value Total bilirubin =< 1.2 times the upper limit of the institutional normal value Absolute neutrophil count (ANC) >= 1,000/ul Platelets >= 100,000/ul Hemoglobin >= 8 g/dl (transfusion- and/or growth factor-dependent patients are not excluded if the above parameters can be achieved with such support) For those patients receiving warfarin (Coumadin), unfractionated heparin, or low-molecular weight heparin therapy, the applicable coagulation parameter that is being monitored must be within the accepted therapeutic ranges for those indications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Z Orlowski
Organizational Affiliation
Alliance for Clinical Trials in Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Palo Alto Medical Foundation-Camino Division
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Christiana Care Health System-Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
MedStar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Holy Cross Hospital
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Jupiter Medical Center
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
Facility Name
Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
AdventHealth Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Kansas City NCI Community Oncology Research Program
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66208
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889-5600
Country
United States
Facility Name
Minneapolis VA Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Missouri Baptist Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States
Facility Name
Center for Cancer Care and Research
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Frisbie Hospital
City
Rochester
State/Province
New Hampshire
ZIP/Postal Code
03867
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Novant Health Presbyterian Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Lenoir Memorial Hospital
City
Kinston
State/Province
North Carolina
ZIP/Postal Code
28501
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Greenville Health System Cancer Institute-Eastside
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Central Vermont Medical Center/National Life Cancer Treatment
City
Berlin
State/Province
Vermont
ZIP/Postal Code
05602
Country
United States
Facility Name
University of Vermont and State Agricultural College
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
Danville Regional Medical Center
City
Danville
State/Province
Virginia
ZIP/Postal Code
24541
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma

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