This phase I trial tests the effects of T-cell receptor (TCR) alpha/beta-depleted blood making (progenitor) cells and CD45RA-depleted donor white blood cells (lymphocytes) in children and young adults with a blood cancer that is in remission but is at high risk of relapse. Giving chemotherapy, such as cyclophosphamide, fludarabine, thiotepa, and melphalan, before a donor (peripheral blood progenitor cell) transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (progenitor cells) to grow. Colony-stimulating factors, such as granulocyte colony-stimulation factor (G-CSF), may increase the production of white blood cells so that the immune system is better able to fight infection. When the healthy stem cells from a related donor, such as TCR alpha/beta-depleted progenitor cells, are infused into a patient they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Giving an infusion of a donor's white blood cells (donor lymphocyte infusion [DLI]), such as CD4RA-depleted DLI, may help the patient's immune system see the remaining cancer cells and destroy them. Antithymocyte globulin (ATG), a gamma globulin, is given to a patient before a transplantation to kill T cells and lower the risk of graft-versus-host disease (GVHD). Giving TCR alpha/beta-depleted progenitor cells with CD4RA-depleted DLI may be safe and tolerable in treating children and young adults with a blood cancer that is in remission but at a high risk of relapse. This trial also evaluates the addition of blinatumomab in patients that have a CD-19 positive cancer. Blinatumomab binds to CD19, which is found on most B cells (a type of white blood cell) and some types of leukemia cells. It also binds to a protein called CD3, which is found on T cells (another type of white blood cell). This may help the immune system kill cancer cells. Blinatumomab is a type of bispecific T-cell engager. Adding blinatumomab to TCR alpha/beta-depleted progenitor cells with CD4RA-depleted DLI may be safe, tolerable and may improve response in children and young adult patients with a CD19 positive blood cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07052370.
Locations matching your search criteria
United States
Tennessee
Memphis
Saint Jude Children's Research HospitalStatus: Active
Contact: Brandon Matthew Triplett
Phone: 901-595-3300
PRIMARY OBJECTIVE:
I. Assess the safety and feasibility of early CD45RA-depleted DLI administration.
SECONDARY OBJECTIVES:
I. Assess the safety and feasibility of the addition of blinatumomab in the early post-transplant period in patients with CD19+ malignancy.
II. To measure and describe the pharmacokinetics of lapine T-lymphocyte immune globulin (rabbit ATG) in hematopoietic cell transplantation (HCT) recipients on this study.
EXPLORATORY OBJECTIVES:
I. Estimate the efficacy of TCR alpha/beta-depleted progenitor cell graft with early memory T-cell DLI, plus selected use of blinatumomab, in haploidentical donor hematopoietic cell transplantation for hematologic malignancies.
II. Estimate the incidence of neutrophil and platelet engraftment, malignant relapse, event-free survival per disease subgroups (e.g. acute lymphoblastic leukemia [ALL] versus [vs] acute myeloid leukemia [AML]), and overall survival at one-year post-transplantation.
III. Estimate incidence and severity of acute and chronic (GVHD).
IV. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
V. Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta spectratyping, and lymphocyte phenotype and function.
VI. Describe the use of early CD45RA-depleted DLI.
VII. Assess and record efficacy of CD45RA-depleted DLI, and all adverse events that are related to CD45RA-depleted DLI.
OUTLINE:
DONOR: Donors receive G-CSF subcutaneously (SC) on days -5 to -1 and day 0 if needed and undergo apheresis on day -1 and additionally on day 0 if needed.
RECIPIENT: Patients receive ATG (rabbit) intravenously (IV) on days -12 to -10, cyclophosphamide IV on day -9, fludarabine IV on days -8 to -4, thiotepa IV twice on day -3, melphalan IV on days -2 and -1 and TCR alpha/beta+ and CD19+ depleted progenitor cells IV over 30 minutes on days 0 and on day 1 if needed. Patients receive G-CSF SC or IV once daily (QD) until absolute neutrophil count (ANC) is > 2000 for 2 consecutive days or as clinically indicated and CD415RA-depleted DLI IV once during days 10-21. Starting at least 4 weeks post-DLI, patients with CD19+ cancers also receive blinatumomab IV continuously over a total of 4 weeks with a 14 day break after the first 2 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection and bone marrow throughout the study.
After completion of study treatment, patients are followed for up to 1 year post-transplantation.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorBrandon Matthew Triplett
