Mini Allo Stem Cell Transplantation for the Treatment of Solid Tumors

• Status: Completed
• Trial end date: 2010-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Beth Israel Deaconess Medical Center
• Collaborator: Amgen

Criteria

Inclusion Criteria

Patients:

• Candidates for this trial will be patients with metastatic solid tumors for whom no standard therapy exists or who have evidence of measurable disease that is clearly progressing following standard biologic therapy or chemotherapy for metastatic disease.

• Patients must have a healthy family member who is HLA-identical to the recipient and who is willing and able to receive a course of G-CSF and undergo 2- 4 daily leukaphereses.

• Each patient must be willing to participate as a research subject and must sign an informed consent form.

• Patients must be ambulatory with good performance status (ECOG 0 or 1; Karnofsky PS 100-80%).

• Patients must have adequate organ function as defined by:

1. WBC > 3000/mm3, plt > 100,000/mm3, and hemoglobin > 10gm/100ml

2. Serum creatinine < 1.8mg/dl or Cr clearance > 60cc/min.

3. Total bilirubin < 1.5mg/dl

4. No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias

5. LVEF ≥40% by echocardiogram or MUGA scan (Patients whose LVEF is between 40% and 50% will have their cyclophosphamide dose reduced by 25% to 45 mg/kg/d for 2 days (total dose of 90 mg/kg).)

6. FEV1 > 2.0 liters or > 75% of predicted for height and age.

• Patients must not be on systemic corticosteroids for intercurrent illness.

• Patients must be between 18 and 60 years of age. Patients over 60 will be accrued on an individual basis with approval of BMT service attendings.

• Women of childbearing potential must have a negative pregnancy test and not become pregnant while on treatment.

Donors:

• Absence of hematologic or marrow function-related diseases that interfere with the collection of sufficient numbers of normal progenitor cells.

• Absence of any medical condition that would pose a serious health risk to a patient undergoing peripheral blood stem cell harvest.

• Negative HIV, HTLV-1, and hepatitis C serologies.

• Negative for hepatitis B surface antigen (NOTE: Donors who are hepatitis B surface antibody and/or core antibody positive BUT hepatitis B surface antigen negative will be considered for transplant.)

• The donor must be a blood relation. Any healthy family member will be considered for marrow donation. Selection of a donor will be based on typing of HLA-A, B, DR loci to be carried out on the recipient, siblings, parents and possibly other family members such as aunts, uncles and cousins. A prospective related donor must be HLA identical to the patient.

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.