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

September 19, 2013 updated by: Oncotherapeutics

A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for Patients With Relapsed or Refractory Multiple Myeloma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Bakersfield, California, United States, 93309-0633
        • Comprehensive Blood and Cancer Center
      • Fresno, California, United States, 93720
        • Hematology-Oncology Medical Group of Fresno, Incorporated
      • West Hollywood, California, United States, 90069
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer and Blood Disorders at Suburban Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose and dose-limiting toxicity

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oncotherapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

April 19, 2006

First Submitted That Met QC Criteria

April 19, 2006

First Posted (Estimate)

April 21, 2006

Study Record Updates

Last Update Posted (Estimate)

September 20, 2013

Last Update Submitted That Met QC Criteria

September 19, 2013

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000479712
  • ONCOTHER-20051780
  • ONCOTHER-424Sm35
  • CYTOGEN-ONCOTHER-20051780

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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