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

Phase 2

Terminated

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

Interventions: Biological: Donor lymphocyte preparation depleted of host functional alloreactive T-cells

Brief 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 .

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

One of the following hematological malignancies:

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.

Arm && Interventions

Group	Intervention	Description
ATIR	Donor lymphocyte preparation depleted of host functional alloreactive T-cells	-

Primary Outcome Measures

Name	Time	Method
Transplant Related Mortality	6, 12 and 24 months after the transplantation	TRM is defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)

Secondary Outcome Measures

Name	Time	Method
Incidence and Severity Graft-versus-host Disease (GVHD)	Up to 24 months after the transplantation	GVHD was graded according to standard criteria as referred to in the reference module (Filipovich et al. 2005; Przepiorka et al. 1995).
Progression Free Survival	Up to 24 months after the transplantation
Incidence and Severity of Bacterial, Viral or Fungal Infection	Up to 24 months after the transplantation
Immune Reconstitution	Up to 24 months after the transplantation
Health Status (Including Quality of Life)	Up to 24 months after the transplantation
Overall Survival	6, 12, and 24 months after the transplantation

Locations (15): Universitair Ziekenhuis Gasthuisberg
🇧🇪
Leuven, Belgium
University of Liege - CHU Sart Tilman
🇧🇪
Liege, Belgium
HHSC, Henderson Hospital Site
🇨🇦
Hamilton, Ontario, Canada
Ontario Cancer Institute / Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Maisonneuve-Rosemont Hospital
🇨🇦
Montreal, Quebec, Canada
Universitätsklinikum Freiburg, Medizinische UNI-Klinik
🇩🇪
Freiburg, Germany
Universitätsklinikums Schleswig-Holstein Campus Kiel
🇩🇪
Kiel, Germany
Universitätsklinikum Mainz
🇩🇪
Mainz, Germany
Perugia University
🇮🇹
Perugia, Italy
Academisch Ziekenhuis Maastricht
🇳🇱
Maastricht, Netherlands
Ohio State University, Comprehesive Cancer Center
🇺🇸
Columbus, Ohio, United States
Algemeen Ziekenhuis Sint-Jan
🇧🇪
Brugge, Belgium
Université Libre de Bruxelles - Institute Jules Bordet
🇧🇪
Brussels, Belgium
Universitätsklinikum Würzburg
🇩🇪
Würzburg, Germany
Hammersmith Hospital
🇬🇧
London, United Kingdom