Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer
Low-dose chemotherapy is easier for the body to tolerate than typical high-dose chemotherapy and involves a shorter period of complete immune suppression.
Donor immune cells called lymphocytes, or T cells, fight residual tumor cells that might have remained in the recipients body after stem cell transplant, in what is called a graft-versus-tumor (GVT) effect.
The immune-suppressing drug sirolimus appears to help prevent graft-versus-host disease (GVHD), a side effect of stem cell transplant in which donated T cells sometimes attack healthy tissues, damaging organs such as the liver, intestines and skin.
Th2 cells are cells collected from the transplant donor and grown in a high concentration of sirolimus.
To determine whether stem cell transplantation using low-dose chemotherapy and sirolimus-generated Th2 cells can cause a remission of advanced kidney cancer.
Patients between 18 and 75 years of age who have kidney cancer that has spread beyond the kidney and who have a tissue-matched sibling stem cell donor.
Patients undergo stem cell transplantation as follows:
- Low-intensity chemotherapy with pentostatin and cyclophosphamide over a 21-day period to reduce the level of the immune system to prepare for the transplant. Pentostatin is given through a vein (intravenous (IV)) on days 1, 8 and 15; cyclophosphamide tablets are taken by mouth for 21 consecutive days.
- Sirolimus tablets, taken by mouth, starting 2 days before the transplant and continuing until 60 days after the transplant.
- IV infusions of stem cells and Th2 cells.
Following the transplant, patients have the following procedures:
- Additional Th2 cell infusions on days 14 and 45 after the transplant.
- Follow-up visits at the National Institutes of Health (NIH) Clinical Center twice a week for the first 6 months after the transplant and then less frequently for at least 5 years to evaluate response to treatment and treatment side effects. Evaluations include a bone marrow aspirate and biopsy 1 month after transplant and periodic blood tests and imaging procedures (e.g., computed tomography (CT) or magnetic resonance imaging (MRI) scans).
|Renal Cell Carcinoma Graft-Versus-Host Disease Engraftment Syndrome||Drug: Pentostatin Drug: Sirolimus Drug: Cyclophosphamide Procedure: Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Procedure: Th2 rapa cells Procedure: Donor Lymphocyte Harvest Procedure: Induction Therapy Procedure: GVHD prophylaxis Procedure: Donor Hematopoietic Stem Cell Harvest||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Low Intensity Allogeneic Hematopoietic Stem Cell Transplantation Therapy of Metastatic Renal Cell Carcinoma Using Early and Multiple Donor Lymphocyte Infusions Consisting of Sirolimus-Generated Donor Th2 Cells|
- Clinical Regression of Metastatic Renal Cell Carcinoma (Partial Response (PR)) or Complete Remission of Tumor (Complete Response (CR)) [ Time Frame: 6 Months Post-Transplant (Day +100) ]Response was assessed by computed tomography measurements and the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest LD recorded since the treatment started or the appearance of one or more new lesions.
- Number of Participants With Adverse Events [ Time Frame: 50 months and 6 days ]Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
|Study Start Date:||March 2008|
|Estimated Study Completion Date:||June 2017|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
A sibling who is 6/6 HLA --matched with the recipient. Donors undergo donor lymphocyte harvest and stem cell mobilization and harvest.
Procedure: Donor Lymphocyte Harvest
ApheresisProcedure: Donor Hematopoietic Stem Cell Harvest
Following lymphocyte harvest, donors for recipients will undergo stem cell mobilization and harvest.
Recipients undergo induction therapy, allogeneic stem cell therapy and GVHD prophylaxis.
Pentostatin: 2- 4mg/m^2(CrCL based dosing) intravenous (IV) on days 1, 8, and 15Drug: Sirolimus
Sirolimus: 4 mg by mouth (PO) on days -3 to +7 post-transplant (No Sirolimus administered after day 7 post-stem cell transplant (SCT))Drug: Cyclophosphamide
Cyclosporine: 2 mg/kg every 12 hours PO or IV starting on day -4 of hematopoietic stem cell transplant (HSCT)Procedure: Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Allogeneic Hematopoietic Stem Cell TransplantProcedure: Th2 rapa cells
Th2 rapa cell TransplantationProcedure: Induction Therapy
Pentostatin and cyclophosphamide (PC) conditioning regimen.Procedure: GVHD prophylaxis
Short course of sirolimus plus maintenance therapy with sirolimus A.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00923845
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Daniel H Fowler, M.D.||National Cancer Institute (NCI)|