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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00088855
First received: August 4, 2004
Last updated: November 19, 2014
Last verified: November 2014

August 4, 2004
November 19, 2014
June 2004
October 2006   (final data collection date for primary outcome measure)
CR+nCR rate [ Time Frame: After 18 weeks (6 courses of treatment) ] [ Designated as safety issue: No ]
Will be estimated with an exact 90% confidence interval.
Not Provided
Complete list of historical versions of study NCT00088855 on ClinicalTrials.gov Archive Site
  • CR+nCR+PR rate [ Time Frame: After 18 weeks (6 courses of treatment) ] [ Designated as safety issue: No ]
    Will be estimated with an exact 90% confidence interval.
  • Maximal response rate [ Time Frame: After 18 weeks (6 courses of treatment) ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicities will be tabulated by type and grade.
  • Progression-free survival [ Time Frame: From on-study date to the date of progression or death, whichever comes first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.
  • Overall survival [ Time Frame: From on-study date to the date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.
  • Changes in IL-6 and MIP-1 [ Time Frame: Baseline to up to day 2 of course 1 ] [ Designated as safety issue: No ]
    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).
Not Provided
Not Provided
Not Provided
 
Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma
Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Drug: pegylated liposomal doxorubicin hydrochloride
    Given IV
    Other Names:
    • CAELYX
    • Dox-SL
    • DOXIL
    • doxorubicin hydrochloride liposome
    • LipoDox
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: 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.
Interventions:
  • Drug: bortezomib
  • Drug: pegylated liposomal doxorubicin hydrochloride
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
55
Not Provided
October 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00088855
NCI-2014-01607, NCI-2014-01607, NCI-2012-02810, CDR377483, CALGB 10301, CALGB-10301, U10CA180821, U10CA031946
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Robert Orlowski Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP