Mini Allo Stem Cell Transplantation for the Treatment of Solid Tumors (MiniSolid)
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|ClinicalTrials.gov Identifier: NCT00997529|
Recruitment Status : Completed
First Posted : October 19, 2009
Last Update Posted : July 18, 2016
A major focus of recent research has been the development of effective ways of sensitizing the patient's immune system to recognize the cancer as foreign. Allogeneic stem cell transplantation represents a novel way of potentially achieving this goal. There is recent evidence that non-myeloablative allogeneic stem cell transplantation provides effective therapy for patients with metastatic renal cell carcinoma. Based on the preliminary reports from other investigators treating patient with breast and ovarian cancer, the investigators of this study would propose treating an expanded cohort of patients with any metastatic solid tumor.
The principal endpoints of the trial will include incidence of durable engraftment, quality of hematopoietic and immune reconstitution, extent of donor chimerism, incidence and severity of acute and chronic graft versus host disease (GVHD), and incidence of long-term disease free survival (DFS). The investigators will evaluate the tumor response of patients with stable or progressive disease post-transplant to donor lymphocyte infusions (DLI). The investigators will also study the effects of DLI on T-cell immunity in the recipients.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Solid Tumor||Drug: nonmyeloablative stem cell transplant||Not Applicable|
The trial is a pilot study in which patients with metastatic solid tumors will undergo non-myeloablative allogeneic hematopoietic stem cell transplantation. Patients whose immunosuppressive therapy has been tapered off, are without GVHD, and have evidence of residual or progressive disease will undergo DLI.
In recent years there have been attempts to harness the graft-versus-tumor effect of allogeneic bone marrow transplant to treat patients with metastatic solid tumors. Researchers at the NIH recently reported on 19 patients with refractory metastatic renal-cell carcinoma who had suitable donors and received a preparative regimen of cyclophosphamide and fludarabine followed by an infusion of a peripheral-blood stem-cell allograft from an HLA-identical sibling or a sibling with a mismatch of a single HLA antigen.49 They note that at the time of the last follow-up, 9 of the 19 patients were alive 287 to 831 days after transplantation (median follow-up: 402 days). Two had died of transplantation-related causes and 8 of progressive disease. In 10 patients (53%) metastatic disease regressed: 3 had a complete response, and 7 had a partial response. The patients who had a complete response remained in remission 27, 25, and 16 months after transplantation. Regression of metastases was delayed, occurring a median of 129 days after transplantation, and often followed the withdrawal of cyclosporine and the establishment of complete donor T-cell chimerism. They concluded that these results were consistent with a graft-versus-tumor effect and that non-myeloablative allogeneic stem cell transplantation can induce sustained regression of metastatic RCCA in patients who have had no response to conventional immunotherapy.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nonmyeloablative Allogeneic Stem Cell Transplantation for the Treatment of Solid|
|Study Start Date :||November 2000|
|Actual Primary Completion Date :||November 2007|
|Actual Study Completion Date :||June 2010|
Drug: nonmyeloablative stem cell transplant
Conditioning includes cytoxan 60mg/kg/d on Days 6 & 5, total dose 120mg/kg, Fludarabine 25mg/m2/d on days -5 to -1, total dose 125mg/m2. Patients with decreased cardiac or liver function pre-transplant will have their dose of cytoxan reduced by 25% - 45 mg/kg/d for 2 days or total dose of 90mg/kg. Patients will receive G-CSF (5ug/kg) to foster engraftment. PBSC progenitors will be mobilized from donor with G-CSF 5ug/kg 2x daily starting 4 days prior to stem cell collection until a target of 5-10 x106 CD34+ cells/kg is reached. Peripheral blood progenitors will be isolated from leukaphereses obtained on Days 5 & 6 with additional collections dependent on cell yields. Peripheral blood from donors will be given to patients 1 day after cytoreduction & immunosuppression. Immunosuppression will be tapered Day +60 if no signs of GVHD. Patients with residual non-regressing disease or mixed chimerism after day 100, who are off immunosuppression & do not have signs of GVHD, will receive a DLI
- To determine the percent 100-day survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic stem cell transplantation (SCT). [ Time Frame: 100 days ]
- To determine the incidence of treatment-related toxicity and acute and chronic graft versus host disease. [ Time Frame: 100 days ]
- To determine the overall survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT. [ Time Frame: 2 years ]
- To evaluate the tumor response in patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT. [ Time Frame: 2 years ]
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): NCT00997529
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||David F McDermott, MD||Beth Israel Deaconess Medical Center|