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

Launched by KIADIS PHARMA · Aug 26, 2009

Keywords

ClinConnect Summary

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 Pharm...

Gender

ALL

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.