Clinical trial NCT00602706: Samarium Sm 153 Lexidronam Pentasodium and High-Dose Melphalan in Treating Patients With Multiple Myeloma Undergoing Stem Cell Transplant
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-01-28
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of toxicity incidents (Phase I)
measure: Proportion of successes (Phase II)
Secondary outcomes:
measure: Number of responses (Phase I)
measure: Overall survival (Phase II)
measure: Progression-free survival (Phase II)
measure: Time to progression (Phase II)
measure: Progressive disease variables
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Angela Dispenzieri, MD
role: STUDY_CHAIR
References: