Dose-ranging Study of a Single Administration of T-cell Add-back Depleted of Host Alloreactive Cells in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor

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 of 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 alloreactive T-cells (ATIR) are administered to the patient 4-6 weeks after the stem cell transplant. This method enables early immune reconstitution while preventing graft-versus-host disease.

Inclusion criteria

• Any of the following hematologic malignancies: very high risk leukemia, acute leukemia, chronic myeloid leukemia (CML), lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS)
• Incompatibility at two to three loci (HLA-A, B and/or DR) or a single DR locus of the unshared haplotype between the donor and recipient
• Life expectancy of at least 3 months
• Satisfactory performance status (ECOG ≤ 2);

Exclusion criteria

• Possibility of performing an allogeneic transplant with an HLA (human leukocyte antigen) matched sibling donor
• Availability of an 6/6 HLA-A, B and DRB1 matched unrelated donor within 2-3 months;
• Pregnancy
• Viral hepatitis (B or C)
• Active serious infectious process
• HIV positivity;
• Systemic dysfunction (cardiac, pulmonary, hepatic and renal) contra-indicating allogeneic stem cell transplantation
• Prior allogeneic transplantation
• Prior autologous transplantation within twelve months of baseline visit
• Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome
• Active central nervous system (CNS) disease at baseline
• Participation in a trial with an investigational agent within 30 days prior to entry in the study
• Malignant cells in circulating peripheral blood (> 25%)
• Other active malignant disease that would severely limit life expectancy