NCT00477815

Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma

A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. 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. A peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving monoclonal antibody therapy together with chemotherapy and autologous peripheral stem cell transplant may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with rituximab, melphalan, and autologous peripheral stem cell transplant in treating patients with previously treated multiple myeloma.

Detailed description

OBJECTIVES: Primary * Determine the safety of rituximab, yttrium Y 90 ibritumomab tiuxetan, high-dose melphalan, and autologous peripheral blood stem cell transplantation in patients with previously treated multiple myeloma. * Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonotypic B-cells at baseline and at B-cell recovery in these patients. Secondary * Determine the response rate and progression factors (time to progression, progression-free survival, and duration of response) in patients treated with this regimen. * Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan. OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan. Patients receive rituximab IV followed by a dosimetry dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day -22. Patients with acceptable biodistribution receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14, high-dose melphalan IV over 1 hour on days -2 and -1, and undergo autologous peripheral blood stem cell transplantation on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 0 and continuing until blood counts recover. Cohorts of 3-6 patients receive escalating doses of yttrium Y 90 ibritumomab tiuxetan 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. Bone marrow, blood, and urine samples are collected at baseline and then periodically during study for biomarker correlative studies. After completion of study treatment, patients are followed every 3 months for 5 years.

Conditions

• Multiple Myeloma and Plasma Cell Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	rituximab	375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)
DRUG	melphalan	100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.
BIOLOGICAL	Stem Cell	greater than or equal to 2 x 106 CD34+/kg by IV
BIOLOGICAL	Sargramostim (GM-CSF)	500 mcg by Subcutaneous QD
RADIATION	90Y-Zevalin	Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.
BIOLOGICAL	111In Zevalin	5.0 mCi by IV

Timeline

• Start date: 2005-05-31
• Primary completion: 2011-07-28
• Completion: 2018-05-07
• First posted: 2007-05-24
• Last updated: 2018-05-14

Locations

1 site across 1 country: United States