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

A Phase I/II Study of 153 Sm EDTMP (Quadramet™) and PS-341 (Velcade®) in Patients With Relapsed or Refractory Multiple Myeloma

RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to cancer cells and not harm normal cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Bortezomib may also make cancer cells more sensitive to radiation therapy. Giving samarium Sm 153 lexidronam pentasodium together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium and to see how well they work in treating patients with relapsed or refractory multiple myeloma.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: bortezomib; Other: immunologic technique; Radiation: samarium Sm 153 lexidronam pentasodium

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium in patients with recurrent or refractory multiple myeloma. (Phase I)
• Determine the safety and tolerability of this regimen in these patients. (Phase II)
• Determine the hematologic response rate in patients treated with this regimen. (Phase II)

Secondary

• Determine the rate of serum immunoglobulin light chain reduction in patients treated with this regimen.
• Assess the in vivo toxicity of this regimen to the progenitor cells by measuring complete blood cell count and micronucleated reticulocyte count in these patients.

OUTLINE: This is a phase I, pilot, open-label, dose-escalation study of bortezomib followed by a phase II study.

• Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV over 1 minute on day 1 and bortezomib IV over 3-5 seconds on days 2 and 5.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.

• Phase II: Patients receive samarium Sm 153 lexidronam pentasodium as in phase I and bortezomib at the MTD determined in phase I .

Patients undergo blood sample collection at baseline and then on days 1-6 for correlative studies. Samples are analyzed for micronucleated reticulocyte count and immunoglobulin free light chain ratio to determine the early effects of treatment.

After completion of study treatment, patients are followed weekly for 7 weeks, monthly for 3 months and then every 3 months for a total of 3 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center

Participation Criteria

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:

• Diagnosis of multiple myeloma

  • Relapsed or refractory disease

• Measurable or evaluable disease as defined by at least 1 of the following:

  • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
  • Monoclonal protein ≥ 200 mg by 24-hour urine electrophoresis
  • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

• Previously treated disease

  • No limit to prior therapy provided there is adequate residual organ function
• Must have undergone hematopoietic stem cell collection (for transplant candidates) OR not considered to be a hematopoietic stem cell transplant candidate

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 (ECOG PS of 3 allowed if secondary only to pain)
• Platelet count ≥ 75,000/mm^3
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
• ANC ≥ 1,000/mm^3
• Creatinine ≤ 3 mg/dL
• Calcium ≤ 15 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study therapy
• No impending long bone fracture
• No other active malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or breast cancer
• No uncontrolled infection
• No known hypersensitivity to any of the components of study drugs
• No other co-morbidity that would preclude study participation

PRIOR CONCURRENT THERAPY:

• Recovered from prior surgery, radiotherapy, or other antineoplastic therapy
• No prior samarium Sm 153 lexidronam pentasodium or strontium chloride Sr 89
• At least 3 weeks since prior myelosuppressive agents
• At least 2 weeks since prior nonmyelosuppressive agents (e.g., thalidomide)

• At least 2 weeks since prior and no concurrent high-dose corticosteroids

  • Chronic steroids (maximum dose of 20 mg/day prednisone or equivalent) allowed for disorders other than myeloma (i.e., adrenal insufficiency or rheumatoid arthritis)
• At least 30 days since prior and no other concurrent investigational therapy
• No concurrent external beam radiotherapy
• No concurrent cytotoxic chemotherapy

• No other concurrent systemic antineoplastic therapy including, but not limited to, any of the following:

  • Immunotherapy
  • Hormonal therapy
  • Monoclonal antibody therapy

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity (Phase I)
Confirmed clinical response (complete response, very good partial response, partial response, or minimal response) (Phase II)

Secondary Outcome Measures

Outcome Measure
Immunoglobulin free light chain response
Changes in complete blood cell count and micronucleated reticulocyte count

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 23, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Estimate): May 11, 2011
• Last Update Submitted That Met QC Criteria: May 10, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Bortezomib; Samarium Sm-153 lexidronam
• Other Study ID Numbers: CDR0000546736; P30CA015083 (U.S. NIH Grant/Contract); MC0585 (Other Identifier: Mayo Clinic Cancer Center); 1586-05 (Other Identifier: Mayo Clinic IRB)