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

An Open-label, Uncontrolled, Multicenter, Multinational Study on the Efficacy and Safety of Administration of Donor Lymphocytes Depleted of Alloreactive T-cells (ATIR), Through the Use of TH9402 and Light Treatment in an ex Vivo Process, in Patients Receiving a CD34-selected Peripheral Blood Stem Cell Graft 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.

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.