Mini Allo Stem Cell Transplantation for the Treatment of Solid Tumors
Condition: Metastatic Solid Tumor
Study type: Interventional

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.
    

Intervention name(s): nonmyeloablative stem cell transplant
Intervention type(s): Drug
Intervention description(s): 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
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stem cell transplant; Non-myeloablative; Metastatic Solid Tumor; Donor Leukocyte Infusion