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Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bortezomib
samarium Sm 153 lexidronam pentasodium
Sponsored by
Oncotherapeutics
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Diagnosed with multiple myeloma by 1 of the following criteria: Meets any 2 of the following major criteria: Plasmacytomas on tissue biopsy Bone marrow plasmacytosis (i.e., > 30% plasma cells) Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour urine protein electrophoresis Plasmacytomas on tissue biopsy AND meets any 1 of the following minor criteria: Presence of monoclonal immunoglobulin at a lesser magnitude than given under above major criteria Lytic bone lesions Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour urine protein electrophoresis AND meets 1 of the following minor criteria: Bone marrow plasmacytosis (i.e., 10-30% plasma cells) Lytic bone lesions Presence of monoclonal immunoglobulin at a lesser magnitude than given under major criteria with bone marrow plasmacytosis (i.e., 10-30% plasma cells) AND meets 1 of the following minor criteria: Lytic bone lesions Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL Measurable disease, defined as a monoclonal immunoglobulin spike of ≥ 1 gm/dL by serum electrophoresis and/or a immunoglobulin spike of ≥ 200 mg by 24-hour urine protein electrophoresis or evidence of lytic bone disease OR Nonmeasurable disease (i.e., patients with nonsecretory or oligosecretory multiple myeloma) Relapsed or refractory disease Relapsed disease following a response or stable disease after prior chemotherapy (e.g., single-agent steroids, vincristine, doxorubicin, and dexamethasone [VAD], or melphalan and prednisone [MP]) or high-dose chemotherapy Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to the most recent chemotherapy with or without systemic corticosteroids No plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS syndrome) No extramedullary myeloma PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy > 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ AST and ALT ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN (unless clearly related to disease) Creatinine clearance ≥ 30 mL/min Creatinine clearance > 15 mL/min and < 30 mL/min due to significant myelomatous involvement of kidneys allowed at discretion of investigator Sodium > 130 mmol/L No ECG evidence of acute ischemia or new conduction system abnormalities No myocardial infarction within the past 6 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL) No New York Hospital Association class III or IV heart failure No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that would preclude study treatment No known HIV history No known active hepatitis B or C viral infection No history of allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib, boron, mannitol, ethylenediaminetetramethylenephosphonic acid (EDTMP), or phosphonates No peripheral neuropathy > grade 1 PRIOR CONCURRENT THERAPY: At least 12 weeks since prior samarium Sm 153 lexidronam pentasodium No more than 1 prior treatment At least 24 weeks since prior strontium chloride Sr 89 No more than 1 prior treatment No major surgery within the past 4 weeks No chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) No corticosteroids (> 10 mg/day prednisone or equivalent) within the past 3 weeks No immunotherapy, antibody therapy, or radiotherapy (except localized radiotherapy) within the past 4 weeks No other concurrent investigational agents No concurrent corticosteroids (≥ 10 mg prednisone or equivalent)

Sites / Locations

  • Comprehensive Blood and Cancer Center
  • Hematology-Oncology Medical Group of Fresno, Incorporated
  • Center for Cancer and Blood Disorders at Suburban Hospital

Outcomes

Primary Outcome Measures

Maximum tolerated dose and dose-limiting toxicity

Secondary Outcome Measures

Response rate (complete, partial, and minimal response)
Time to disease progression and time to response
Progression-free and overall survival
Antitumor effects

Full Information

First Posted
April 19, 2006
Last Updated
September 19, 2013
Sponsor
Oncotherapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00316940
Brief Title
Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2007
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Oncotherapeutics

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Radioactive substances, such as samarium 153, may release radiation as it breaks down and kill cancer cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also make tumor cells more sensitive to radiation. Giving samarium 153 together with bortezomib may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of samarium 153 when given together with bortezomib in treating patients with relapsed or refractory multiple myeloma.
Detailed Description
OBJECTIVES: Primary Assess the safety and tolerability (maximum tolerated dose and dose-limiting toxicity) of samarium Sm 153 lexidronam pentasodium and bortezomib in patients with relapsed or refractory multiple myeloma. Secondary Determine the response rate (combined complete response, partial response, and minimal response) in patients treated with this regimen. Determine the time to response and the time to progression of disease in patients treated with this regimen. Determine the progression-free survival and overall survival of patients treated with this regimen. Assess the antitumor effects of this regimen in these patients. OUTLINE: This is an open-label, dose-escalation study of samarium Sm 153 lexidronam pentasodium. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and samarium Sm 153 lexidronam pentasodium IV on day 3. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of samarium Sm 153 lexidronam pentasodium until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The MTD of samarium Sm 153 lexidronam pentasodium is determined with 2 different doses of bortezomib. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Radiation
Intervention Name(s)
samarium Sm 153 lexidronam pentasodium
Primary Outcome Measure Information:
Title
Maximum tolerated dose and dose-limiting toxicity
Secondary Outcome Measure Information:
Title
Response rate (complete, partial, and minimal response)
Title
Time to disease progression and time to response
Title
Progression-free and overall survival
Title
Antitumor effects

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosed with multiple myeloma by 1 of the following criteria: Meets any 2 of the following major criteria: Plasmacytomas on tissue biopsy Bone marrow plasmacytosis (i.e., > 30% plasma cells) Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour urine protein electrophoresis Plasmacytomas on tissue biopsy AND meets any 1 of the following minor criteria: Presence of monoclonal immunoglobulin at a lesser magnitude than given under above major criteria Lytic bone lesions Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour urine protein electrophoresis AND meets 1 of the following minor criteria: Bone marrow plasmacytosis (i.e., 10-30% plasma cells) Lytic bone lesions Presence of monoclonal immunoglobulin at a lesser magnitude than given under major criteria with bone marrow plasmacytosis (i.e., 10-30% plasma cells) AND meets 1 of the following minor criteria: Lytic bone lesions Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL Measurable disease, defined as a monoclonal immunoglobulin spike of ≥ 1 gm/dL by serum electrophoresis and/or a immunoglobulin spike of ≥ 200 mg by 24-hour urine protein electrophoresis or evidence of lytic bone disease OR Nonmeasurable disease (i.e., patients with nonsecretory or oligosecretory multiple myeloma) Relapsed or refractory disease Relapsed disease following a response or stable disease after prior chemotherapy (e.g., single-agent steroids, vincristine, doxorubicin, and dexamethasone [VAD], or melphalan and prednisone [MP]) or high-dose chemotherapy Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to the most recent chemotherapy with or without systemic corticosteroids No plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS syndrome) No extramedullary myeloma PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy > 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ AST and ALT ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN (unless clearly related to disease) Creatinine clearance ≥ 30 mL/min Creatinine clearance > 15 mL/min and < 30 mL/min due to significant myelomatous involvement of kidneys allowed at discretion of investigator Sodium > 130 mmol/L No ECG evidence of acute ischemia or new conduction system abnormalities No myocardial infarction within the past 6 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL) No New York Hospital Association class III or IV heart failure No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that would preclude study treatment No known HIV history No known active hepatitis B or C viral infection No history of allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib, boron, mannitol, ethylenediaminetetramethylenephosphonic acid (EDTMP), or phosphonates No peripheral neuropathy > grade 1 PRIOR CONCURRENT THERAPY: At least 12 weeks since prior samarium Sm 153 lexidronam pentasodium No more than 1 prior treatment At least 24 weeks since prior strontium chloride Sr 89 No more than 1 prior treatment No major surgery within the past 4 weeks No chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) No corticosteroids (> 10 mg/day prednisone or equivalent) within the past 3 weeks No immunotherapy, antibody therapy, or radiotherapy (except localized radiotherapy) within the past 4 weeks No other concurrent investigational agents No concurrent corticosteroids (≥ 10 mg prednisone or equivalent)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James R. Berenson, MD
Organizational Affiliation
Oncotherapeutics
Official's Role
Principal Investigator
Facility Information:
Facility Name
Comprehensive Blood and Cancer Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309-0633
Country
United States
Facility Name
Hematology-Oncology Medical Group of Fresno, Incorporated
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
City
West Hollywood
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Center for Cancer and Blood Disorders at Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19188182
Citation
Berenson JR, Yellin O, Patel R, Duvivier H, Nassir Y, Mapes R, Abaya CD, Swift RA. A phase I study of samarium lexidronam/bortezomib combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin Cancer Res. 2009 Feb 1;15(3):1069-75. doi: 10.1158/1078-0432.CCR-08-1261.
Results Reference
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Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

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