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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Procedure: peripheral blood stem cell transplantation; Drug: melphalan; Biological: sargramostim; Procedure: autologous hematopoietic stem cell transplantation; Radiation: samarium Sm 153 lexidronam pentasodium

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 Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Number of toxicity incidents (Phase I)
Proportion of successes (Phase II)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): June 1, 2003
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 24, 2008
• First Posted (Estimate): January 28, 2008

Study Record Updates

• Last Update Posted (Estimate): May 16, 2011
• Last Update Submitted That Met QC Criteria: May 13, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Sargramostim; Samarium Sm-153 lexidronam
• Other Study ID Numbers: CDR0000582552; P30CA015083 (U.S. NIH Grant/Contract); MC9981 (Other Identifier: Mayo Clinic Cancer Center); 1046-99 (Other Identifier: Mayo Clinic IRB)