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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00477815
Recruitment Status : Completed
First Posted : May 24, 2007
Last Update Posted : May 14, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief 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.

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

Detailed Description:



  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma
Actual Study Start Date : May 31, 2005
Actual Primary Completion Date : July 28, 2011
Actual Study Completion Date : May 7, 2018

Arm Intervention/treatment
Experimental: Rituximab + Zevalin
Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.
Biological: rituximab
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 antigen

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.
Other Name: Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8

Biological: 111In Zevalin
5.0 mCi by IV

Primary Outcome Measures :
  1. Toxicity as measured by CTCAE v 3.0 [ Time Frame: 19 Months ]
  2. Clonotypic B cells [ Time Frame: 19 months ]

Secondary Outcome Measures :
  1. Response (complete response, very good partial response, partial response) [ Time Frame: 19 months ]
  2. Time to progression and duration of response [ Time Frame: 5 years ]
  3. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00477815

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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
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Study Chair: Angela Dispenzieri, MD Mayo Clinic

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Responsible Party: Mayo Clinic Identifier: NCT00477815     History of Changes
Other Study ID Numbers: CDR0000546732
P30CA015083 ( U.S. NIH Grant/Contract )
MC048A ( Other Identifier: Mayo Clinic Cancer Center )
449-05 ( Other Identifier: Mayo Clinic IRB )
NCI-2009-01399 ( Registry Identifier: NCI-CTRO )
021-03-ZEV ( Other Identifier: Biogen IDEC protocol )
106-P148 ( Other Identifier: Biogen IDEC protocol )
First Posted: May 24, 2007    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Keywords provided by Mayo Clinic:
stage I multiple myeloma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents