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

NCT00316940 | Completed Phase 1

• 4 other identifiers: CDR0000479712ONCOTHER-20051780ONCOTHER-424Sm35CYTOGEN-ONCOTHER-20051780
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and dose-limiting toxicity

Secondary Outcomes (4)

• Response rate (complete, partial, and minimal response)

• Time to disease progression and time to response

• Progression-free and overall survival

• Antitumor effects

Interventions

bortezomib DRUG

samarium Sm 153 lexidronam pentasodium RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Oncotherapeutics: lead

Study Sites (4)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309-0633, United States

Location

Hematology-Oncology Medical Group of Fresno, Incorporated

Fresno, California, 93720, United States

Location

Unknown Facility

West Hollywood, California, 90069, United States

Location

Center for Cancer and Blood Disorders at Suburban Hospital

Bethesda, Maryland, 20817, United States

Location

Related Publications (1)

• 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.

  PMID: 19188182 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; samarium Sm-153 lexidronam

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• James R. Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 19, 2006
• First Posted: April 21, 2006
• Study Start: December 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: February 1, 2011
• Last Updated: September 20, 2013

Record last verified: 2007-12

Locations

US (4)