Overview

This trial is active, not recruiting.

Condition multiple myeloma and plasma cell neoplasm
Treatments rituximab, melphalan, stem cell, sargramostim (gm-csf), 90y-zevalin, 111in zevalin
Phase phase 1
Target CD20
Sponsor Mayo Clinic
Collaborator National Cancer Institute (NCI)
Start date May 2005
End date May 2016
Trial size 42 participants
Trial identifier NCT00477815, 021-03-ZEV, 106-P148, 449-05, CDR0000546732, MC048A, NCI-2009-01399, P30CA015083

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.
rituximab Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigen
375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)
melphalan
100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.
stem cell
greater than or equal to 2 x 106 CD34+/kg by IV
sargramostim (gm-csf)
500 mcg by Subcutaneous QD
90y-zevalin Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8
Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.
111in zevalin
5.0 mCi by IV

Primary Outcomes

Measure
Toxicity as measured by CTCAE v 3.0
time frame: 19 Months
Clonotypic B cells
time frame: 19 months

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants from 18 years up to 120 years old.

DISEASE CHARACTERISTICS: - Diagnosis of multiple myeloma - Previously treated disease - Candidate for high-dose chemotherapy with melphalan and autologous stem cell transplantation - No definite evidence of myelodysplasia on pretreatment bone marrow by morphology or by chromosome analysis (e.g., monosomy 7) - Chromosome abnormalities from the myeloma clone allowed PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - ANC ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Bilirubin ≤ 2.0 mg/dL - Alkaline phosphatase ≤ 3 times upper limit of normal (ULN) - AST ≤ 3 times ULN - Creatinine ≤ 2 times ULN - LVEF ≥ 45% - Corrected pulmonary diffusion capacity ≥ 50% - No uncontrolled infection - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No other active malignancy (with the exception of nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiation therapy - No HIV positivity PRIOR CONCURRENT THERAPY: - More than 3 weeks since prior myelosuppressive chemotherapy, except cyclophosphamide pulsing for stem cell collection) - No other concurrent immunotherapy, radiotherapy, chemotherapy or antimyeloma therapy - Concurrent chronic corticosteroids at doses of prednisone ≤ 20 mg per day (or equivalent) allowed - Concurrent adjuvant hormonal therapy (e.g., tamoxifen citrate or leuprolide acetate) allowed

Additional Information

Official title A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Mayo Clinic.