Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)
The goal of this clinical research study is to learn if adding Zevalin (ibritumomab tiuxetan) to low-intensity chemotherapy (the combination of rituximab, bendamustine, and fludarabine), followed by an allogeneic stem cell transplant, can help to control lymphoma. The safety of this combination will also be studied.
Two (2) forms of ibritumomab tiuxetan will be used in this study. 90Y-ibritumomab tiuxetan is designed to attach to lymphoma cells and destroy the cells using a radioactive particle that is attached to it. 111In-ibritumomab tiuxetan is like 90Y- ibritumomab tiuxetan, but the radioactive particle that is attached to it does not kill lymphoma cells. The radioactive particle makes the drug able to be seen inside your body. It is being used in this study to predict how fast the study drug will travel in the body and how long the drug stays in the body.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells.
Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.
|Leukemia Lymphoma||Drug: Rituximab Drug: 111In Ibritumomab Procedure: Planar Scintigraphy Imaging Drug: 90Y IbritumomabTiuxetan Drug: Fludarabine Drug: Bendamustine Drug: Thymoglobulin Drug: Tacrolimus Drug: Methotrexate Drug: Mycophenolate Drug: G-CSF Procedure: Stem Cell Transplantation||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Dose-Intense Yttrium-90 Ibritumomab Tiuxetan (Zevalin)-Containing Non-Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in B-cell Malignancies|
- 100 Day Treatment-Related Mortality (TRM) [ Time Frame: 100 days ]The method of Thall, Simon, and Estey used to monitor the TRM rate within the first 100 days during the course of the trial. Computed Tomography (CT), Positron Emission Tomography (PET) scans, and bone marrow biopsy/aspirate to check the status of the disease.
- Overall Survival (OS) [ Time Frame: From date of treatment to date of relapse or death, up to 3 years ]Percentage of participants alive at 3 years, estimated using method of Kaplan and Meier. Overall survival calculated from date of transplant to date of relapse or death.
|Actual Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2019|
|Estimated Primary Completion Date:||January 2019 (Final data collection date for primary outcome measure)|
Experimental: Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
250 mg/m2 by vein preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively on Days -22 and -14.
Other Name: RituxanDrug: 111In Ibritumomab
(5.0 mCi +/- 10% of 111In) by vein immediately following the infusion of rituximab on Day -22.
Other Name: ZevalinProcedure: Planar Scintigraphy Imaging
Day -22, -21 to -16: Planar scintigraphy whole-body imaging started on Day -22 post 111In Ibritumomab infusion prior to voiding, and repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Whole-body planar scintigraphy imaging will be repeated between 22-26 hours, then between 70-74 hours, and later between 142-146 hours post 111In Ibritumomab injection.Drug: 90Y IbritumomabTiuxetan
Calculated to deliver not below 10 Gy to normal organs (liver, lungs, kidneys) by vein post rituximab on Day -14.
Other Name: ZevalinDrug: Fludarabine
30 mg/m2 intravenously on Days -5, -4, and -3.
Other Names:Drug: Bendamustine
130 mg/m2 intravenously on D-5, -4 and -3.
Other Names:Drug: Thymoglobulin
1 mg/kg (based on actual body weight) on Days -2 and -1 will be administrated to patients receiving a cord blood (CB) and a matched unrelated donor (MUD).
Other Names:Drug: Tacrolimus
Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no Graft versus Host Disease (GVHD) is present.
For patients receiving cord blood (CB) graft, the Graft versus Host Disease (GvHD) prophylaxis will be with Tacrolimus. Tacrolimus will start on D-2 administrated at starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on D -2 and will be tapered around Day +180 if no GvHD is present.
Other Name: PrografDrug: Methotrexate
5 mg/m2 by vein on Day +1, +3 and +6. Patients receiving an unrelated graft will also be given methotrexate on Day +11 after the transplant.Drug: Mycophenolate
15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth administered from Days -3 to +45 and then tapered to end by day 100 if there is no Graft versus Host Disease (GVHD).
Other Names:Drug: G-CSF
5 mcg/kg/day subcutaneously beginning Day +7 for patients receiving related and matched unrelated donor (MUD) grafts and on Day 0 for patients receiving a cord blood (CB). G-CSF will continue until the absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
Other Names:Procedure: Stem Cell Transplantation
Stem Cell Transplantation on Day 0
Other Name: Allogeneic transplantation
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01490723
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Issa F. Khouri, MD,BS||M.D. Anderson Cancer Center|