Samarium Sm 153 Lexidronam Pentasodium Combined With Zoledronic Acid or Pamidronate in Treating Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00482378
First received: June 4, 2007
Last updated: March 24, 2014
Last verified: March 2014

June 4, 2007
March 24, 2014
March 2005
September 2014   (final data collection date for primary outcome measure)
  • Toxicity (Phase I) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Confirmed clinical response of serum and urine monoclonal protein (Phase II) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Toxicity (Phase I)
  • Confirmed clinical response of serum and urine monoclonal protein (Phase II)
Complete list of historical versions of study NCT00482378 on ClinicalTrials.gov Archive Site
  • Response (Phase I) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Bone pain response (Phase II) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Toxicity (Phase II) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Response (Phase I)
  • Bone pain response (Phase II)
  • Toxicity (Phase II)
Not Provided
Not Provided
 
Samarium Sm 153 Lexidronam Pentasodium Combined With Zoledronic Acid or Pamidronate in Treating Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain
An Open-Label, Pilot Study of Samarium - Sm 153 Lexidronam (Quadramet) in Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain

RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to cancer cells and not harm normal cells. Zoledronic acid and pamidronate may help relieve bone pain caused by multiple myeloma. Giving samarium Sm 153 lexidronam pentasodium together with zoledronic acid or pamidronate may be an effective treatment for multiple myeloma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of samarium Sm 153 lexidronam pentasodium when given together with zoledronic acid or pamidronate and to see how well it works in treating patients with relapsed or refractory multiple myeloma and bone pain.

OBJECTIVES:

Primary

  • Determine the safety and tolerability of samarium Sm 153 lexidronam pentasodium in combination with zoledronic acid or pamidronate disodium in patients with relapsed or refractory multiple myeloma and bone pain. (Phase I)
  • Determine the clinical response in patients treated with these regimens. (Phase II)

Secondary

  • Determine the effect of these regimens on changes in patient-reported bone pain levels.

OUTLINE: This is a multicenter, open-label, pilot, phase I, dose-escalation study of samarium Sm 153 lexidronam pentasodium followed by a phase II study.

  • Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV over 1 minute on day 1. Patients also receive zoledronic acid IV over 15 minutes or pamidronate disodium IV over 2-4 hours on day 1 and then monthly thereafter 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 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive samarium Sm 153 lexidronam pentasodium at the MTD determined in phase I and zoledronic acid or pamidronate disodium as in phase I.

Bone pain is assessed periodically.

After completion of study treatment, patients are followed every 3-6 months for up to 3 years.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Pain
  • Drug: Pamidronate
    90 mg by IV monthly.
    Other Name: Aredia
  • Drug: Zoledronic acid
    4 mg by IV monthly.
    Other Name: Zometa
  • Radiation: Sm 153 lexidronam
    0.5 mCi/kg or 1 mCi/kg by IV.
    Other Name: Sm 153 lexidronam consists of radioactive samarium and a tetraphosphonate chelator, ethylenediaminetetramethylenephosphonic acid (EDTMP).
Experimental: Sm 153 lexidronam
Interventions:
  • Drug: Pamidronate
  • Drug: Zoledronic acid
  • Radiation: Sm 153 lexidronam
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
39
Not Provided
September 2014   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Relapsed or refractory disease, meeting 1 of the following criteria:

      • Recurrent disease after stem cell transplantation
      • Recurrent or progressive disease despite treatment with ≥ 1 standard regimen (e.g., an alkylating agent plus glucocorticoid and/or the combination of vincristine, doxorubicin hydrochloride, and dexamethasone)
  • Measurable or evaluable disease, defined by at least 1 of the following:

    • Monoclonal protein ≥ 1.0 g by serum 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)
  • Patients must have already undergone hematopoietic stem cell collection, if believed to be a transplant candidate OR not eligible for a hematopoietic stem cell transplant

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if secondary to pain)
  • ANC ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 8.0 g/dL (transfusions allowed)
  • 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 active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix or breast
  • No uncontrolled infection
  • No other co-morbidity that would interfere with the patient's ability to participate in this trial
  • No known hypersensitivity to any of the components of samarium Sm 153 lexidronam pentasodium or bisphosphonates

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior surgery, radiotherapy, or other antineoplastic therapy
  • More than 4 weeks since prior melphalan or other myelosuppressive agents
  • More than 2 weeks since prior nonmyelosuppressive agents (e.g., thalidomide or high-dose corticosteroids)
  • More than 30 days since prior and no other concurrent investigational therapy
  • No prior samarium Sm 153 lexidronam pentasodium or strontium chloride Sr 89
  • No concurrent external beam radiotherapy
  • No concurrent high-dose corticosteroids

    • Concurrent chronic steroids (maximum dose of 20 mg/day prednisone equivalent) allowed for disorders other than myeloma (i.e., adrenal insufficiency or rheumatoid arthritis)
    • Low-dose steroids allowed for replacement or inhalation therapy
  • No other concurrent medications, including any of the following:

    • Cytotoxic chemotherapy
    • Systemic antineoplastic therapy including, but not limited to, immunotherapy, hormonal therapy, or monoclonal antibody therapy
    • Prophylactic hematopoietic growth factors

      • Hematopoietic growth factors allowed for established cytopenia therapy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00482378
CDR0000546769, P30CA015083, MC048B, 261-05
Yes
Angela Dispenzieri, M.D., Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Angela Dispenzieri, M.D. Mayo Clinic
Mayo Clinic
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP