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

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.