Clinical trial NCT00482378: Samarium Sm 153 Lexidronam Pentasodium Combined With Zoledronic Acid or Pamidronate in Treating Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain
Official title: An Open-Label, Pilot Study of Samarium - Sm 153 Lexidronam (Quadramet) in Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Pain
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
pain
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-05
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Toxicity (Phase I)
timeFrame: 12 weeks
measure: Confirmed clinical response of serum and urine monoclonal protein (Phase II)
timeFrame: 12 weeks
Secondary outcomes:
measure: Response (Phase I)
timeFrame: 12 weeks
measure: Bone pain response (Phase II)
timeFrame: 12 weeks
measure: Toxicity (Phase II)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Angela Dispenzieri, M.D.
role: STUDY_CHAIR
References: