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
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Pain
Drug: Pamidronate
Drug: Zoledronic acid
Radiation: Sm 153 lexidronam
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Pilot Study of Samarium - Sm 153 Lexidronam (Quadramet) in Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 39
Study Start Date: March 2005
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sm 153 lexidronam 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).

Detailed Description:

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.

  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, 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
  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: NCT00482378

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Angela Dispenzieri, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Angela Dispenzieri, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00482378     History of Changes
Other Study ID Numbers: CDR0000546769, P30CA015083, MC048B, 261-05
Study First Received: June 4, 2007
Last Updated: March 24, 2014
Health Authority: United States: Federal Government

Keywords provided by Mayo Clinic:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
pain

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Zoledronic acid
Samarium ethylenediaminetetramethylenephosphonate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014