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Donor Partial Immune Cell Depletion for the Treatment of Hematologic Malignancies
Trial Status: active
This trial studies how well donor stem cell transplantation with alpha/beta T cell and B cell depletion (partial Immune Cell Depletion) works in treating patients with hematologic malignancies. Alpha/beta T cell and B cell depletion is a new method of cell processing for stem cell transplants with an unrelated donor or partially matched related donor using the CliniMACS device. There is a higher rate of complications using cells from an unrelated or partially matched related donor. T cells within the donor cells may cause a complication called graft versus host disease, where the transplanted cells from a donor can attack the body's normal cells. Donated B cells can sometimes be infected with a virus (Epstein Bar Virus or EBV) which may result in the development of enlarged lymph nodes (lymphoproliferative disorder). Alpha/beta T cell and B cell depletion may reduce some of the complications of the transplant and decrease the time it takes for the new stem cells to grow in the body.
Inclusion Criteria
Disease eligibility
* Leukemias/lymphomas:
** Acute myeloid leukemia, primary or secondary
*** Disease status: remission or =<10% bone marrow blasts
** Myelodysplasia
** Acute lymphoblastic leukemia
*** Disease status: in hematologic remission
** Chronic myelogenous leukemia:
*** Disease status: chronic phase, accelerated phase or blast crisis now in second chronic phase.
** Mixed lineage or biphenotypic acute leukemia
** Lymphoblastic lymphoma
*** Disease status: remission
** Burkitt’s lymphoma/leukemia:
***Disease status: in remission
Evaluation of organ status as per Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) standard operating procedure (SOP)
No active untreated infection. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic
Signed consent by parent/guardian or able to give consent if >= 18 years
Negative pregnancy test for females of childbearing potential
DONOR
Unrelated donor meets National Marrow Donor Program criteria for donation
* Infectious disease testing
* CHOP BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases
Donor matching. High resolution typing at all loci to be performed
* Unrelated:
** Up to one antigen mismatch A, B or DR
** One antigen mismatch at class I and one allele mismatch at another class I locus
** Donor and collection center willing to undergo mobilization and apheresis
* Related donor:
** Human leukocyte antigen (HLA) match, other than sibling
** One-two allele or antigen mismatch
** Haploidentical parent or other related donor
** Donor must be willing to undergo granulocyte colony-stimulating factor (G-CSF) mobilization and stem cell apheresis
Exclusion Criteria
Patients who do not meet disease, organ or infectious criteria
No suitable donor
Received previous allogeneic transplant
Additional locations may be listed on ClinicalTrials.gov for NCT02323867.
I. Evaluate engraftment of patients receiving unrelated donor or partially matched related donor peripheral stem cells that have been alpha/beta T cell depleted and CD19+ B cell depleted using the CliniMACS device.
Ia. Evaluate primary non-engraftment.
Ib. Evaluate engraftment kinetics (time to absolute neutrophil count [ANC] > 500, platelets > 20 x 10^9/l).
II. Estimate incidence and extent of acute and chronic graft versus (vs.) host disease.
IIa. Overall acute graft versus host disease (GVHD) incidence.
IIb. Incidence of grade IV acute GVHD.
IIc. Incidence of chronic GVHD.
III. Assess incidence treatment-related mortality (TRM).
IV. Assess probability of one year leukemia free survival (LFS).
V. Assess tempo of immune reconstitution.
Va. Assess incidence of viral infections, including cytomegalovirus (CMV), adenovirus, human herpesvirus (HHV)6 and Epstein-Barr virus (EBV).
Vb. Assess tempo of lymphocyte reconstitution and recovery of T cell receptor excision circle (TREC)s.
VI. Pre-transplant evaluation will include killer cell immunoglobulin-like receptors (KIR) typing of the patient and donor.
OUTLINE: Patients receive 1 of 2 total body irradiation (TBI) conditioning regimens or a non-TBI conditioning regimen.
TBI CONDITIONING REGIMEN I: Patients receive thymoglobulin (ATG) intravenously (IV) on days -11 to -9 and undergo TBI over 6 fractions on days -8 to -6. Patients also receive thiotepa IV over 2 hours on days -5 to -4 and cyclophosphamide IV over 2 hours on days -3 to -2.
TBI CONDITIONING REGIMEN II: Patients receive ATG IV on days -9 to -7, thiotepa IV over 2 hours on days -7 to -6, cyclophosphamide IV over 2 hours on days -5 to -4, and undergo TBI over 6 fractions on days -3 to -1.
NON-TBI CONDITIONING REGIMEN: Patients receive busulfan IV on days -9 to -6, ATG IV on days -9 to -7, thiotepa IV over 2 hours on days -5 to -4, cyclophosphamide IV over 2 hours on days -3 to -2.
After all conditioning regimen, patients undergo hematopoietic stem cell transplantation (HCST) with alpha/beta T-cell/CD19+ B-cell-depleted unrelated or partially matched donor-derived allogeneic peripheral blood stem cells on day 0, and EBV positive patients receive rituximab on day 1.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationChildren's Hospital of Philadelphia
