Bortezomib and Pegylated Liposomal Doxorubicin in Treating Patients With 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: December 6, 2013
Last verified: December 2013
  Purpose

This phase II trial is studying how well giving bortezomib together with liposomal doxorubicin works in treating patients with multiple myeloma. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining bortezomib with liposomal doxorubicin may kill more cancer cells.


Condition Intervention Phase
Extramedullary Plasmacytoma
Isolated Plasmacytoma of Bone
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: bortezomib
Drug: pegylated liposomal doxorubicin hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete plus near-complete (CR + nCR) response rate [ Time Frame: 126 days ] [ Designated as safety issue: No ]
    Evaluated using the criteria of Blade et al. with the additional category or near-CR as defined by Richardson et al. Estimated with an exact 90% confidence interval.


Secondary Outcome Measures:
  • CR+nCR+PR rate [ Time Frame: 126 days ] [ Designated as safety issue: No ]
    Evaluated using the criteria of Blade et al. with the additional category or near-CR as defined by Richardson et al. Estimated with an exact 90% confidence interval.

  • Toxicity rates using the CTCAE version 3.0 [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Tabulated by type and grade.

  • Progression-free survival [ Time Frame: From onstudy date to the date of progression or death, whichever comes first, assessed up to 7 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Overall survival [ Time Frame: From onstudy date to the date of death, assessed up to 7 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.


Estimated Enrollment: 55
Study Start Date: June 2004
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib, pegylated doxorubicin HCl liposome)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and pegylated doxorubicin HCl liposome 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.
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

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the complete response (CR) + near-complete response (nCR) rate of the bortezomib /pegylated liposomal doxorubicin 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. Data for minor responses (MR) and stable disease (SD), as well as progressive disease (PD) will be collected as well.

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. Data will also be collected about the engraftment characteristics of those patients who undergo transplantation, including the number of days to achieve an ANC of 500, a platelet count of 100,000, and packed red blood cell and platelet transfusion independence.

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 IV over 3-5 seconds on days 1, 4, 8, and 11 and pegylated doxorubicin HCl liposome 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.

Patients are followed every 6 weeks for 2 years and then every 6 months for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of symptomatic multiple myeloma with evaluable disease parameters
  • 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
  • Non-pregnant and Non-nursing

    • Inclusion of females of childbearing potential requires a negative pregnancy test
  • 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 HIV-seropositive and are taking anti-retrovirals may not participate in this study because of potential interactions between these medications and the investigational agent; 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; active disease is defined as patients with a known viral hepatitis whose liver function tests are elevated beyond the criteria indicated
  • No 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 (RNV or MUGA)
  • No Class 3 or Class 4 New York Heart Association Congestive Heart Failure
  • Creatinine < 2.5 mg/dL
  • ALT (SGPT) and AST (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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088855

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Orlowski Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088855     History of Changes
Other Study ID Numbers: NCI-2012-02810, NCI-2012-02810, CDR377483, CALGB-10301, CALGB-10301, U10CA031946
Study First Received: August 4, 2004
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Bortezomib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 15, 2014