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

NCT ID: NCT00088855

Last Updated: 2019-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-06-15

Study Completion Date

2008-01-08

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (bortezomib and pegylated liposomal doxorubicin)

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.

Group Type EXPERIMENTAL

Bortezomib

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pegylated Liposomal Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Interventions

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Bortezomib

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pegylated Liposomal Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Other Intervention Names

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[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade 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

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Z Orlowski

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

Jupiter Medical Center

Jupiter, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Minneapolis VA Medical Center

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Center for Cancer Care and Research

St Louis, Missouri, United States

Site Status

Frisbie Hospital

Rochester, New Hampshire, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Lenoir Memorial Hospital

Kinston, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

Danville Regional Medical Center

Danville, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2014-01607

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02810

Identifier Type: -

Identifier Source: secondary_id

CDR377483

Identifier Type: -

Identifier Source: secondary_id

CALGB 10301

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-10301

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2014-01607

Identifier Type: -

Identifier Source: org_study_id

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