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

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00477815

Purpose

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 killl 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	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: melphalan Drug: rituximab Drug: yttrium Y 90 ibritumomab tiuxetan Procedure: autologous hematopoietic stem cell transplantation Procedure: laboratory biomarker analysis Procedure: peripheral blood stem cell transplantation	Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Melphalan Rituximab Ibritumomab tiuxetan Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity as measured by CTCAE v 3.0 [ Designated as safety issue: Yes ]
Clonotypic B cells [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response (complete response, very good partial response, partial response) [ Designated as safety issue: No ]
Time to progression and duration of response [ Designated as safety issue: No ]
Impact of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	May 2005
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477815

Locations

United States, Arizona
Mayo Clinic Scottsdale	Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Florida
Mayo Clinic - Jacksonville	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Angela Dispenzieri, MD	Mayo Clinic
Investigator:	Thomas E. Witzig, MD	Mayo Clinic
Investigator:	Morie A. Gertz, MD	Mayo Clinic
Investigator:	Philip R. Greipp, MD	Mayo Clinic
Investigator:	Martha Q. Lacy, MD	Mayo Clinic
Investigator:	John A. Lust, MD, PhD	Mayo Clinic
Investigator:	S. V. Rajkumar, MD	Mayo Clinic
Investigator:	Steve Zeldenrust, MD	Mayo Clinic
Investigator:	Suzanne Hayman, MD	Mayo Clinic
Investigator:	Stephen J. Russell, MD, PhD	Mayo Clinic
Investigator:	Shaji K. Kumar, MD	Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000546732, MAYO-MC048A, MAYO-IRB-449-05
Study First Received:	May 23, 2007
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00477815
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I multiple myeloma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Study placed in the following topic categories:

Melphalan
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Rituximab
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias
Hemostatic Disorders

Multiple Myeloma
Antibodies, Monoclonal
Antibodies
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Immunoglobulins
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Therapeutic Uses
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009