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

NCT ID: NCT00482378

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-21
• Study Completion Date: 2008-12-02

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm; Pain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sm 153 lexidronam

Group Type: EXPERIMENTAL

Pamidronate

Intervention Type: DRUG

90 mg by IV monthly.

Zoledronic acid

Intervention Type: DRUG

4 mg by IV monthly.

Sm 153 lexidronam

Intervention Type: RADIATION

0.5 mCi/kg or 1 mCi/kg by IV.

Interventions

Pamidronate

90 mg by IV monthly.

Intervention Type: DRUG

Zoledronic acid

4 mg by IV monthly.

Intervention Type: DRUG

Sm 153 lexidronam

0.5 mCi/kg or 1 mCi/kg by IV.

Intervention Type: RADIATION

Other Intervention Names

Aredia; Zometa; Sm 153 lexidronam consists of radioactive samarium and a tetraphosphonate chelator, ethylenediaminetetramethylenephosphonic acid (EDTMP).

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Dispenzieri, M.D.

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC048B

Identifier Type: OTHER

Identifier Source: secondary_id

261-05

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000546769

Identifier Type: -

Identifier Source: org_study_id