Bortezomib in Treating Patients With Newly Diagnosed High-Risk Stage III Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00075881
First received: January 9, 2004
Last updated: November 27, 2012
Last verified: October 2012
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with newly diagnosed high-risk stage III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Plasma Cell Neoplasm
Drug: PS-341
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response Rate on Induction [ Time Frame: participants were evaluated prior to each cycle, up to 8 cycles with a median number of 6 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    Eastern Cooperative Oncology Group (ECOG) Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 42 eligible and treated patients were included in the analysis.


Secondary Outcome Measures:
  • Response Rate on Maintenance [ Time Frame: participants were evaluated prior to each cycle, up to 45 cycles with a median number of 9 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    ECOG Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 15 eligible and treated patients were included in the analysis.

  • Response Rate on Reinduction [ Time Frame: participants were evaluated prior to each cycle, up to 23 cycles with a median number of 3 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    ECOG Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 7 eligible and treated patients were included in the analysis.

  • 1-year Progression Free Survival Probability [ Time Frame: Every 3 months if patient is <2 years from study entry, every 6 months if patient is 2-6 years from study entry, no specific requirment if patient is more than 6 years from study entry ] [ Designated as safety issue: No ]
    Progression-free survival is defined as time from randomization to disease progression or death from any cause, whichever occurred first. Disease progression is defined using the ECOG Myeloma Response Criteria. Kaplan-Meier method is used to estimate the 1-year progression-free survival probability. 42 eligible and treated patients were included in the analysis.


Enrollment: 44
Study Start Date: January 2004
Study Completion Date: May 2011
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PS-341

Induction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose. Repeat cycles every 3 weeks for a total of 8 cycles.

Maintenance treatment: PS-341 1.3 mg/m2 IV push days 1 and 15

Reinduction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose.

Drug: PS-341

Induction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose. Repeat cycles every 3 weeks for a total of 8 cycles.

Maintenance treatment: PS-341 1.3 mg/m2 IV push days 1 and 15

Reinduction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose.

Other Names:
  • Bortezomib
  • Velcade
  • MLN-341
  • LDP-341

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with newly diagnosed high-risk stage III multiple myeloma treated with bortezomib induction therapy.

Secondary

  • Determine the progression-free survival of patients treated with this drug.
  • Determine the response rate and duration of second response in patients who relapse or progress while on maintenance therapy and subsequently receive reinduction therapy with this drug.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression must complete at least 2 courses of induction therapy. Patients who achieve complete remission receive 2 additional courses, but no more than 8 courses total, and then proceed to maintenance therapy.
  • Maintenance therapy: Patients receive bortezomib IV over 3-5 seconds on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may return to induction therapy (reinduction therapy).
  • Reinduction therapy: Patients receive bortezomib as in induction therapy. Courses repeat every 3 weeks until second disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years from study entry.

ACTUAL ACCRUAL: A total of 44 patients were accrued for this study.

  Eligibility

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

Inclusion Criteria

  • Diagnosis of multiple myeloma meeting the following criteria:

    • Symptomatic disease diagnosed within the past 30 days
    • Measurable or evaluable disease meeting at least 1 of the following criteria:

      • Serum monoclonal protein ≥ 1 g/dL (measurable disease)
      • Monoclonal light chain in urine protein electrophoresis ≥ 200 mg/24-hour urine collection (measurable disease)
      • Bone marrow plasmacytosis ≥ 30% (evaluable disease)
  • High-risk disease, defined by ≥ 1 of the following criteria:

    • Beta 2-microglobulin ≥ 5.5 μg/mL
    • Plasma cell labeling index ≥ 1%
    • Deletion of chromosome 13 by cytogenetic analysis
  • Age>=18
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (ECOG performance status of 3 allowed if secondary to acute bone event [i.e., fracture])
  • Adequate hematopoietic,hepatic, renal, cardiovascular function:

    • Platelet count ≥ 20,000/mm^3 (transfusion allowed)
    • Hemoglobin ≥ 7.0 g/dL (transfusion allowed)
    • Absolute neutrophil count ≥ 500/mm^3 (without growth factor support)
    • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 times ULN
    • Alkaline phosphatase ≤ 2.5 times ULN
    • Creatinine clearance ≥ 20 mL/min
  • Fertile patients must use effective contraception
  • Concurrent corticosteroids allowed for treatment of chronic disorders other than multiple myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)
  • Prior or concurrent bisphosphonates allowed
  • Concurrent localized radiotherapy allowed upon approval by study chair

Exclusion criteria:

  • Pregnant or nursing
  • Positive pregnancy test
  • Myocardial infarction within the past 6 months
  • New York Heart Association class III or IV heart failure
  • Uncontrolled angina
  • Acute ischemia by electrocardiography (EKG)
  • Severe uncontrolled ventricular arrhythmias
  • Active conduction system abnormalities by EKG
  • Cardiac amyloidosis
  • Poorly controlled hypertension
  • History of allergic reaction attributable to compounds containing boron or mannitol
  • Greater than grade 1 peripheral neuropathy
  • Other serious medical or psychiatric illness that would preclude study completion
  • Prior biologic therapy for multiple myeloma
  • Concurrent biologic therapy
  • Concurrent pegfilgrastim
  • Prior chemotherapy for multiple myeloma
  • Concurrent chemotherapy
  • Prior radiotherapy for multiple myeloma
  • Less than 4 weeks since prior radiotherapy for plasmacytoma (e.g., solitary plasmacytoma)
  • Other concurrent antineoplastic therapy for multiple myeloma
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00075881

  Show 92 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Angela Dispenzieri, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Dispenzieri A, Zhang L, Fonseca R, et al.: Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02). [Abstract] Blood 108 (11): A-3527, 2006.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075881     History of Changes
Other Study ID Numbers: CDR0000349450, U10CA021115, E2A02
Study First Received: January 9, 2004
Results First Received: March 8, 2012
Last Updated: November 27, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage III multiple myeloma
high risk, newly diagnosed multiple myeloma

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

ClinicalTrials.gov processed this record on April 17, 2014