This phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing a subset of the T cells from the donor cells before transplant may stop this from happening.
OUTLINE: CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed up for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Given IV
Correlative studies
Given IV
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Given IV or PO
Given IV
Undergo TBI
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Graft Failure
Graft failure defined as failure to reach ANC of \>500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to \<100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure
Time frame: Up to 5 years
Time to Discontinuation of Systemic Immunosuppression
Measure the number of days to discontinuation of systemic immunosuppression (both including and excluding calcineurin inhibitors) in pediatric recipients of CD45RA+ T cell-depleted PBSCT. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)
Time frame: 5 years post transplant
Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion
Number of days post-transplant without transfusion where platelet count is \>50,000/uL. Measured as the first of three days
Time frame: Up to 5 years
Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion
Number of days post transplant until platelet count is \>20,000/uL for three consecutive days without transfusion, counted as the first of three days
Time frame: Up to 5 years
Time to ANC of > 1,000/uL
Time (in days) to ANC of \> 1,000/uL, counted as the first of three consecutive days post-transplant
Time frame: Up to 5 years
Time to ANC of > 500/uL
Time (in days) to ANC of \> 500/uL, counted as the first of three consecutive days post-transplant
Time frame: Up to 5 years
Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression
Number of patients with chronic GVHD defined using NIH criteria. Incidents requiring only calcineurin inhibitors will not be counted. If patients do not develop cGVHD after transplant but then relapse and then receive a donor lymphocyte infusion or antigen specific T cells as treatment, they will no longer be evaluable for the cGVHD endpoint.
Time frame: Up to 5 years
Acute GVHD Grade III-IV
Number of patients with acute GVHD grade III-IV
Time frame: Up to day 100
Acute GVHD Grades II-IV
Number of patients with acute GVHD grades II-IV
Time frame: Up to day 100
Steroid Refractory Acute GVHD
Presence of steroid refractory acute GVHD within the first 100 days post transplant
Time frame: Up to day 100
Relapse Post-transplant
Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology
Time frame: Up to 5 years
Transplant Related Mortality
Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse
Time frame: Up to 5 years
Use of Additional Immune Suppressive Agents to Treat Chronic GVHD
Use of additional immune suppressive agents to treat chronic GVHD other than first line therapy. First line therapy is considered prednisone and tacrolimus/cyclosporin.
Time frame: Up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.