Mini Allo Stem Cell Transplantation for the Treatment of Solid Tumors

Not Applicable

Completed

• Conditions: Metastatic Solid Tumor
• Interventions: Drug: nonmyeloablative stem cell transplant

• Registration Number: NCT00997529
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2000-11
• Primary Completion: 2007-11
• Study First Submitted: 2008-05-05
• Study First Submitted QC: 2009-10-16
• Study First Posted: 2009-10-19
• Study Completion: 2010-06
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-14
• Last Update Posted: 2016-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Patients:

• Patients with brain metastases, leptomeningeal disease or seizure. (NOTE: Patients with a history of brain metastases must be 6 months from definitive therapy (i.e. surgery or radiation) and have no evidence of disease or edema on brain CT scan or MRI.)
• Female patients who are pregnant or breast-feeding
• ECOG performance status >1. (Karnofsky PS <80%) (See Appendix 1.)
• Left ventricular ejection fraction of < 40%.
• Active viral (e.g. chronic active hepatitis), bacterial or fungal infection.
• Patients seropositive for HIV, HTLV -1,
• Patients not providing informed consent.
• Patients with known hypersensitivity to E. coli-derived products.

Donors:

• A positive HIV or HTLV-1 test or evidence of active/persistent viral hepatitis infection will exclude the donor from participation in this study. Donors who are HIV or HTLV-1 positive are ineligible because of the risk of transmission of virus during peripheral blood stem cell transplantation. Presence of any medical condition that would pose a serious health risk by undergoing peripheral blood stem cell harvest. Known hypersensitivity to E. coli-derived products.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	nonmyeloablative stem cell transplant	-

Primary Outcome Measures

Name	Time	Method
To determine the percent 100-day survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic stem cell transplantation (SCT).	100 days
To determine the incidence of treatment-related toxicity and acute and chronic graft versus host disease.	100 days

Secondary Outcome Measures

Name	Time	Method
To determine the overall survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT.	2 years
To evaluate the tumor response in patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT.	2 years

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States