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

Mayo Clinic

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Drug: melphalan; Biological: sargramostim; Radiation: samarium Sm 153 lexidronam pentasodium

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00602706

P30CA015083 (U.S. NIH Grant/Contract)

1046-99 (Other Identifier)

CDR0000582552

MC9981 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 76 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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