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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00478075
First received: May 23, 2007
Last updated: May 10, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Other: immunologic technique
Radiation: samarium Sm 153 lexidronam pentasodium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of 153 Sm EDTMP (Quadramet™) and PS-341 (Velcade®) in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Confirmed clinical response (complete response, very good partial response, partial response, or minimal response) (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunoglobulin free light chain response [ Designated as safety issue: No ]
  • Changes in complete blood cell count and micronucleated reticulocyte count [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: September 2005
Study Completion Date: June 2009
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478075

Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Angela Dispenzieri, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Angela Dispenzieri, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00478075     History of Changes
Other Study ID Numbers: CDR0000546736, P30CA015083, MC0585, 1586-05
Study First Received: May 23, 2007
Last Updated: May 10, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory 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
Samarium ethylenediaminetetramethylenephosphonate
Bortezomib
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014