Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy

This study is currently recruiting patients.

Sponsored by

National Heart, Lung, and Blood Institute (NHLBI)

Purpose

We have already demonstrated graft-versus-tumor (GVT) effects using non-myeloablative allogeneic stem cell transplantation in two existing protocols: for melanoma (98-H-0006) and renal cell carcinoma (RCC)(97-H-0196). The main objective of this study is to identify other metastatic neoplasms which may be susceptible to the GVT effect. We will treat patients with progressive metastatic solid tumors refractory to standard therapy with a non-myeloablative allogeneic PBSC transplant from a family donor. A GVT effect from immunocompetent donor immune cells could extend life expectancy and possibly cure such patients. Eligible patients are treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will infuse lymphocytes in patients with <100% donor T-cell chimerism or with evidence of tumor progression in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect, respectively. This trial is open to all types of metastic, treatment-refractory, solid neoplasms other than malignant melanoma and RCC. The trial design permits up to 10 patients with a specific tumor type to be enrolled to screen for anti-tumor effects. A single complete response in a specific tumor type is an indication to exclude further patients with that diagnosis from the study. Subsequently, a new protocol which focuses on further defining a GVT effect in that disease category will be instituted.

Study Type: Clinical Trial

Official Title: Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy

Further Study Details: We have already demonstrated graft-versus-tumor (GVT) effects using non-myeloablative allogeneic stem cell transplantation in two existing protocols: for melanoma (98-H-0006) and renal cell carcinoma (RCC)(97-H-0196). The main objective of this study is to identify other metastatic neoplasms which may be susceptible to the GVT effect.  We will treat patients with progressive metastatic solid tumors refractory to standard therapy with a non-myeloablative allogeneic PBSC transplant from a family donor. A GVT effect from immunocompetent donor immune cells could extend life expectancy and possibly cure such patients.  Eligible patients are treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will infuse lymphocytes in patients with <100% donor T-cell chimerism or with evidence of tumor progression in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect, respectively.  This trial is open to all types of metastic, treatment-refractory, solid neoplasms other than malignant melanoma and RCC. The trial design permits up to 10 patients with a specific tumor type to be enrolled to screen for anti-tumor effects. A single complete response in a specific tumor type is an indication to exclude further patients with that diagnosis from the study. Subsequently, a new protocol which focuses on further defining a GVT effect in that disease category will be instituted.  

Eligibility

Genders Eligible for Study:  Both Criteria

PATIENTS:

Patients with metastatic solid tumors (excluding RCC and malignant melanoma) which are histologically confirmed, progressive and incurable. Melanoma and renal cell patients will be enrolled on studies 98-H-0006 and 97-H-0196 respectively.

No known standard therapy for the patient's disease that is potentially curative or definately capable of extending life expectancy.

Metastatic disease which is bidimensionally evaluable radiographically.

No prior treatment for neoplasm within 30 days.

Informed consent given.

Availability of HLA identical or single HLA-locus mismatched family donor.

Willingness and availability to return to the NIH for scheduled follow-ups.

Must not be pregnant or lactating.

Age 10 to 80 years of age.

Must not have an ECOG performance status of 3 or more. Must not have psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.

No major anticipated illness or organ failure incompatible with survival from PBSC transplant.

Must not have DLCO: <40% predicted.

Must not have left ventricular ejection fraction: <30%.

Must not have serum creatinine > 2.5mg/dl.

Must not have serum bilirubin >4 mg/dl, transaminases > 5x upper limit of normal.

Must not have oral intake < 1,200 calories/day.

Must not have recent weight loss of greater than or equal to 10% of actual body weight.

Must not have life expectancy < 3 months

Must not have therapy for malignancy within 4 weeks of beginning protocol.

Must not have CNS metastatic disease associated with intracranial bleeding, uncontrolled seizure disorder or significant intracranial mass effect.

Must not have other malignant diseases liable to relapse or progress within 5 years.

Must not have uncontrolled infection.

DONOR:

HLA identical or single HLA-locus mismatched family donor, up to 80 years old.

Informed consent given.

Must not be pregnant or lactating.

Donor must be fit to receive G-CSF and undergo apheresis. (No uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).

HIV negative donor. Donors who are positive for HBV, HCV or

HTLV -I may be used at the discretion of the investigator.

Location and Contact Information

Maryland

National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike   Bethesda,   Maryland,    20892,   United States; Recruiting

PRPL     Warren G. Magnuson Clinical Center National Institutes of Health   Bethesda,    Maryland,   20892-4754,   United States  1-800-411-1222    prpl@mail.cc.nih.gov  

More Information

Detailed Web Page

Publications that lead up to this study

Eibl. 1996. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer, Blood, Vol. 88, p. 1501

Or. 1998. Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study, Cytokines Cell Mol Ther, Vol. 4, p. 1

Ueno. 1998. Allogeneic periperal-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer, J Clin Oncol, Vol. 16, p. 986

Study ID Numbers  99-H-0064

NLM Identifier  NCT00001880

Date study started March 11, 1999

Recruitment status verified  April 28, 2000

Last Updated  April 28, 2000

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