Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma
|ClinicalTrials.gov Identifier: NCT00477815|
Recruitment Status : Active, not recruiting
First Posted : May 24, 2007
Last Update Posted : August 29, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma and Plasma Cell Neoplasm||Biological: rituximab Drug: melphalan Biological: Stem Cell Biological: Sargramostim (GM-CSF) Radiation: 90Y-Zevalin Biological: 111In Zevalin||Phase 1|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma|
|Study Start Date :||May 2005|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||May 2018|
U.S. FDA Resources
Experimental: Rituximab + Zevalin
Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.
375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)
Other Name: Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigenDrug: 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 IVBiological: Sargramostim (GM-CSF)
500 mcg by Subcutaneous QDRadiation: 90Y-Zevalin
Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.
Other Name: Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8Biological: 111In Zevalin
5.0 mCi by IV
- Toxicity as measured by CTCAE v 3.0 [ Time Frame: 19 Months ]
- Clonotypic B cells [ Time Frame: 19 months ]
- Response (complete response, very good partial response, partial response) [ Time Frame: 19 months ]
- Time to progression and duration of response [ Time Frame: 5 years ]
- Impact of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan [ Time Frame: 1 week ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00477815
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Angela Dispenzieri, MD||Mayo Clinic|