efficacy and safety of a donor lymphocyte preparation depleted of functional host alloreactive t-cells (atir) in patients undergoing a peripheral blood stem cell transplant from a related, haploidentical donor

Conditions: Myeloid Leukemia; Lymphoblastic Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Disorders

Summary: the purpose of this study is to determine whether the administration of a donor lymphocyte preparation depleted of functional host alloreactive t-cells (atir) after a t-cell depleted stem cell transplant from a related, haploidentical donor enhances survival by improving the immune effect against infections while preventing graft-versus-host disease .

allogeneic stem cell transplantation is the treatment of choice for many patients with leukemia and other hematologic malignancies. however, a major limitation of this therapy is that for a significant number of patients no fully hla-matched donor can be found. the application of partially hla-matched (haploidentical) family donors, who are virtually always available, has some complications. if there is no t-cell add-back it increases the risk for life-threatening infections and disease relapse, while in case of t-cell add-back the risk for graft-versus-host disease is raised. kiadis pharma has developed a method to selectively deplete host alloreactive t-cells through photodynamic therapy, using th9402 ex vivo. the donor lymphocyte preparation depleted of functional host alloreactive t-cells (atir) is administered to the patient 28-42 days after the stem cell transplant.

Eligibility criteria:
inclusion criteria: one of the following hematological malignancies: * acute myeloid leukemia (aml) * acute lymphoblastic leukemia (all) * myelodysplastic syndrome (mds) * ph-positive chronic myeloid leukemia (cml) * non-hodgkin lymphoma (nhl) * myelodysplastic syndrome (mds) * chronic myeloid leukemia (cml) * multiple myeloma (mm) * chronic lymphocytic leukemia (cll) * myeloproliferative syndrome (mps) exclusion criteria: * aml in 1st complete remission with good risk karyotypes * mm featuring concurrent extramedullar disease or being non-responsive to prior therapy * cml in blast crisis * cll concurrently transformed into high-grade lymphoma and failing to demonstrate at least partial remission * nhl with concurrent bulky disease (≥ 5 cm) * diffusing capacity for carbon monoxide (dlco) \< 40% predicted * left ventricular ejection fraction \< 40% * ast/sgot \> 2.5 x uln * bilirubin \> 1.5 x uln * creatinine \> 1.5 x uln * hiv positive * positive pregnancy test for women of childbearing age * prior haploidentical peripheral blood stem cell or cord blood transplantation * less than 2 years from a prior allogeneic stem cell transplantation * estimated probability of surviving less than three months * major anticipated illness or organ failure incompatible with survival from transplant * severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible * known allergy to any of the components of atir * any other condition which, in the opinion of the investigator, makes the patient ineligible for the study donor inclusion criteria: * haploidentical family donor with 2 to 3 mismatches at the hla-a, -b and/or dr loci of the unshared haplotype. * male or female, age ≥ 16, ≤ 75 years. * donors must be fit to receive g-csf and undergo apheresis (normal blood count, normotensive and no history of stroke). * donor must have eastern cooperative oncology group (ecog) performance status of 2 or less. * donor must provide written informed consent. donor exclusion criteria: * medically uncontrolled coronary heart disease. * myocardial infarction within the last 3 months. * history of uncontrolled seizures. * history of malignancy (except basal cell or squamous carcinoma of the skin, positive pap smear and subsequent negative follow up). * positive test result for any of the mandatory viral tests in the applicable region, except for a positive cytomegalovirus (cmv) result, which does not lead to exclusion. * presence of a transmissible disease (such as hiv positive), a major illness, a suspected systemic dysfunction and/or an active inflammatory or autoimmune disorder. * female donors who are pregnant or nursing.

Keywords: haploidentical stem cell transplantation graft-versus-host disease immune reconstitution alloreactive t-cells photodepletion th9402 transplant related mortality hematologic malignancy