Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Bortezomib

Samarium Sm-153 lexidronam

Analgesics, Non-Narcotic

bortezomib

samarium Sm 153 lexidronam pentasodium

James R. Berenson, MD

RATIONALE: Radioactive substances, such as samarium 153, may release radiation as it breaks down and kill cancer cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also make tumor cells more sensitive to radiation. Giving samarium 153 together with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of samarium 153 when given together with bortezomib in treating patients with relapsed or refractory multiple myeloma.

OBJECTIVES:

Primary

* Assess the safety and tolerability (maximum tolerated dose and dose-limiting toxicity) of samarium Sm 153 lexidronam pentasodium and bortezomib in patients with relapsed or refractory multiple myeloma.

Secondary

* Determine the response rate (combined complete response, partial response, and minimal response) in patients treated with this regimen.
* Determine the time to response and the time to progression of disease in patients treated with this regimen.
* Determine the progression-free survival and overall survival of patients treated with this regimen.
* Assess the antitumor effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of samarium Sm 153 lexidronam pentasodium.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and samarium Sm 153 lexidronam pentasodium IV on day 3. Treatment repeats every 8 weeks for up to 4 courses 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 6 patients experience dose-limiting toxicity. The MTD of samarium Sm 153 lexidronam pentasodium is determined with 2 different doses of bortezomib.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for Patients With Relapsed or Refractory Multiple Myeloma

Oncotherapeutics

immunologic technique

Angela Dispenzieri, MD

RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to cancer cells and not harm normal cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Bortezomib may also make cancer cells more sensitive to radiation therapy. Giving samarium Sm 153 lexidronam pentasodium together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium and to see how well they work in treating patients with relapsed or refractory multiple myeloma.

OBJECTIVES:

Primary

* Determine the maximum tolerated dose of bortezomib when given together with samarium Sm 153 lexidronam pentasodium in patients with recurrent or refractory multiple myeloma. (Phase I)
* Determine the safety and tolerability of this regimen in these patients. (Phase II)
* Determine the hematologic response rate in patients treated with this regimen. (Phase II)

Secondary

* Determine the rate of serum immunoglobulin light chain reduction in patients treated with this regimen.
* Assess the in vivo toxicity of this regimen to the progenitor cells by measuring complete blood cell count and micronucleated reticulocyte count in these patients.

OUTLINE: This is a phase I, pilot, open-label, dose-escalation study of bortezomib followed by a phase II study.

* Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV over 1 minute on day 1 and bortezomib IV over 3-5 seconds on days 2 and 5.

Cohorts of 3-6 patients receive escalating doses of bortezomib 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 as in phase I and bortezomib at the MTD determined in phase I .

Patients undergo blood sample collection at baseline and then on days 1-6 for correlative studies. Samples are analyzed for micronucleated reticulocyte count and immunoglobulin free light chain ratio to determine the early effects of treatment.

After completion of study treatment, patients are followed weekly for 7 weeks, monthly for 3 months and then every 3 months for a total of 3 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Samarium Sm 153 Lexidronam Pentasodium and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase I/II Study of 153 Sm EDTMP (Quadramet™) and PS-341 (Velcade®) in Patients With Relapsed or Refractory Multiple Myeloma

National Cancer Institute (NCI)

Mayo Clinic

Angela Dispenzieri

Molgramostim

Sargramostim

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

sargramostim

melphalan

autologous hematopoietic stem cell transplantation

peripheral blood stem cell transplantation

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.

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.

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

Angela Dispenzieri, M.D.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT00316940	Multiple Myelom...	bortezomib samarium Sm 153...	18 Years -	National Cancer Institute (NCI)
Samarium Sm 153 Lexidronam Pentasodium and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT00478075	Multiple Myelom...	bortezomib immunologic tec... samarium Sm 153...	18 Years -	Mayo Clinic
Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT00316940	Multiple Myelom...	bortezomib samarium Sm 153...	18 Years -	National Cancer Institute (NCI)
Samarium 153 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT00316940	Multiple Myelom...	bortezomib samarium Sm 153...	18 Years -	National Cancer Institute (NCI)
Samarium Sm 153 Lexidronam Pentasodium and High-Dose Melphalan in Treating Patients With Multiple Myeloma Undergoing Stem Cell Transplant	NCT00602706	Multiple Myelom...	sargramostim melphalan autologous hema... peripheral bloo... samarium Sm 153...	18 Years -	Mayo Clinic
Samarium Sm 153 Lexidronam Pentasodium and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT00478075	Multiple Myelom...	bortezomib immunologic tec... samarium Sm 153...	18 Years -	Mayo Clinic
Samarium Sm 153 Lexidronam Pentasodium and High-Dose Melphalan in Treating Patients With Multiple Myeloma Undergoing Stem Cell Transplant	NCT00602706	Multiple Myelom...	sargramostim melphalan autologous hema... peripheral bloo... samarium Sm 153...	18 Years -	Mayo Clinic

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