Samarium Sm 153 Lexidronam Pentasodium and High-Dose Melphalan in Treating Patients With Multiple Myeloma Undergoing Stem Cell Transplant

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00602706

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

126

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Samarium Sm 153 lexidronam pentasodium contains a radioactive substance that kill cancer cells. Peripheral blood stem cell transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy and radioactive drugs used to kill cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of samarium Sm 153 lexidronam pentasodium when given together with high-dose melphalan in treating patients with multiple myeloma undergoing stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: sargramostim Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: samarium Sm 153 lexidronam pentasodium	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

To find the maximum tolerated dose of samarium Sm 153 lexidronam pentasodium when given with fixed high-dose melphalan as a conditioning regimen for autologous peripheral blood stem cell transplantation in patients with multiple myeloma. (Phase I)
To assess the response rates of this regimen in these patients. (Phase II)

OUTLINE: This is a 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 once between days -14 and -10. Patients also receive melphalan IV on day -1. Patients undergo peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover.
Phase II: Patients receive samarium Sm 153 lexidronam pentasodium at the MTD determined in phase I .

Blood samples are collected periodically to determine clearance of samarium Sm 153 lexidronam pentasodium and bone marrow dosimetry.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Primary Purpose:

Treatment

Official Title:

A Phase I/II Dose Escalation Study Assessing the Toxicity and Efficacy of 153-Samarium-EDTMP in Place of TBI in the Conditioning Regimen for PBSCT for Patients With Multiple Myeloma

Study Start Date :

Jan 1, 2000

Actual Primary Completion Date :

Jun 1, 2003

Actual Study Completion Date :

Jul 1, 2010

Outcome Measures

Primary Outcome Measures

Number of toxicity incidents (Phase I) []
Proportion of successes (Phase II) []

Secondary Outcome Measures

Number of responses (Phase I) []
Overall survival (Phase II) []
Progression-free survival (Phase II) []
Time to progression (Phase II) []
Progressive disease variables []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma requiring treatment
Must have at least 2 x 10^6 CD34+ cells collected for peripheral blood stem cell transplantation

PATIENT CHARACTERISTICS:

Inclusion criteria:

ECOG performance status (PS) 0-2 (ECOG PS > 2 allowed if secondary to neuropathy or acute bone event)
Direct bilirubin ≤ 2.0 mg/dL
Alkaline phosphatase ≤ 750 μ/L
Creatinine ≤ 3.0 mg/dL
Ejection fraction ≥ 45%
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for 6 months after the completion of study therapy

Exclusion criteria:

DLCO < 50%
FVC < 50%
FEV_1 < 50%
Active malignancy with the exception of nonmelanoma skin cancer
Uncontrolled infection
NYHA class III-IV cardiac disease

PRIOR CONCURRENT THERAPY:

May or may not have received prior chemotherapy
At least 3 weeks since prior chemotherapy
Cyclophosphamide pulsing for stem cell collection allowed
At least 4 weeks since prior biologic therapy
At least 2 weeks since prior bisphosphonates and bisphosphonates maybe resumed 1 month post-study treatment