Yttrium Y 90 Ibritumomab Tiuxetan, Rituximab, Indium In-111 Ibritumomab Tiuxetan, Fludarabine, Melphalan, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT00577278|
Recruitment Status : Active, not recruiting
First Posted : December 20, 2007
Last Update Posted : November 13, 2017
RATIONALE: Giving monoclonal antibody therapy, radioimmunotherapy, and chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor that do not exactly match the patient's blood, are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and sirolimus before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects and how well giving indium In 111 ibritumomab tiuxetan and yttrium y 90 ibritumomab tiuxetan together with rituximab, fludarabine, melphalan, and donor stem cell transplant works in treating patients with B-cell non-Hodgkin lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease Leukemia Lymphoma||Biological: rituximab Drug: fludarabine phosphate Drug: melphalan Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Radiation: indium In 111 ibritumomab tiuxetan Radiation: yttrium Y 90 ibritumomab tiuxetan Other: laboratory biomarker analysis||Phase 2|
PRIMARY OBJECTIVES: I. To evaluate the safety and efficacy of a preparative regimen of Yttrium-90 (90^Y)- labeled anti-cluster of differentiation (CD)20 monoclonal antibody (MAb) (yttrium Y 90 ibritumomab tiuxetan) in combination with fludarabine (fludarabine phosphate) and melphalan followed by allogeneic hematopoietic stem cell transplant (APBSCT) for treatment of patients with B-cell low-grade non-Hodgkin lymphoma (LG NHL), intermediate-grade non-Hodgkin lymphoma (IG NHL) and mantle cell lymphoma (MCL). II. To evaluate the short- and long-term complications of this new preparative regimen, including rates of engraftment, acute and chronic graft-versus-host-disease (GVHD) and infectious complications. III. To estimate the disease response rate, disease relapse (progression) rate, and non-relapse mortality rate. IV. To perform exploratory studies that seek to measure/characterize the expression of costimulatory molecules and impact of these molecules on the natural killer (NK) and T cells of a subset of lymphoma patients pre- post- allogeneic stem cell transplant (ASCT) and the stem cell product from a portion of sibling donors.
OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive rituximab intravenously (IV) followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4.
STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for B-Cell Non-Hodgkin Lymphoma Using Zevalin, Fludarabine and Melphalan|
|Actual Study Start Date :||January 15, 2007|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||April 2018|
Experimental: Treatment (chemo, monoclonal antibody therapy, transplant)
REDUCED-INTENSITY CONDITIONING: Patients receive rituximab IV followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper.
Other Names:Drug: fludarabine phosphate
Other Names:Drug: melphalan
Other Names:Drug: sirolimus
Other Names:Drug: tacrolimus
Given PO or IV
Other Names:Procedure: allogeneic hematopoietic stem cell transplantation
Undergo APBSCTRadiation: indium In 111 ibritumomab tiuxetan
Other Name: IDEC-In2B8Radiation: yttrium Y 90 ibritumomab tiuxetan
Other Names:Other: laboratory biomarker analysis
- Relapse/progression rate [ Time Frame: At 2 years ]Confidence intervals will be established by calculating the exact 95% confidence limits for a binomial parameter. The product-limit method of Kaplan and Meier will be utilized.
- Relapse-free survival [ Time Frame: 5 years from transplant ]The product-limit method of Kaplan and Meier will be utilized. Will consider univariate Cox models.
- Progression-free survival [ Time Frame: 5 years from transplant ]The product-limit method of Kaplan and Meier will be utilized. Will consider univariate Cox models.
- Toxicity and safety of treatment regimen [ Time Frame: 5 years after transplant ]Will be summarized in terms of type, severity (by National Cancer Institute [NCI] Common Toxicity Criteria [CTC] and nadir or maximum values for the laboratory measure) and time of onset. Analyses will be conducted to evaluate acute and chronic GVHD and infectious complications.
- Overall survival [ Time Frame: 5 years from transplant ]The product-limit method of Kaplan and Meier will be utilized. Will consider univariate Cox models.
- Duration of response [ Time Frame: 5 years from transplant ]
- Time-to-progression (TTP) [ Time Frame: 5 years from transplant ]
- Non-relapse mortality [ Time Frame: 5 years from transplant ]
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 ClinicalTrials.gov identifier (NCT number): NCT00577278
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010-3000|
|Study Chair:||Auayporn P. Nademanee, MD||City of Hope Medical Center|