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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00967343
Other study ID # CR-AIR-004
Secondary ID EudraCT no. 2008
Status Terminated
Phase Phase 2/Phase 3
First received
Last updated
Start date August 2009
Est. completion date February 2012

Study information

Verified date May 2021
Source Kiadis Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 .


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 information / eligibility

Status Terminated
Enrollment 40
Est. completion date February 2012
Est. primary completion date February 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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.

Study Design


Intervention

Biological:
Donor lymphocyte preparation depleted of host functional alloreactive T-cells
Single intravenous infusion with 2x10E6 T-cells/kg

Locations

Country Name City State
Belgium Algemeen Ziekenhuis Sint-Jan Brugge
Belgium Université Libre de Bruxelles - Institute Jules Bordet Brussels
Belgium Universitair Ziekenhuis Gasthuisberg Leuven
Belgium University of Liege - CHU Sart Tilman Liege
Canada HHSC, Henderson Hospital Site Hamilton Ontario
Canada Maisonneuve-Rosemont Hospital Montreal Quebec
Canada Ontario Cancer Institute / Princess Margaret Hospital Toronto Ontario
Germany Universitätsklinikum Freiburg, Medizinische UNI-Klinik Freiburg
Germany Universitätsklinikums Schleswig-Holstein Campus Kiel Kiel
Germany Universitätsklinikum Mainz Mainz
Germany Universitätsklinikum Würzburg Würzburg
Italy Perugia University Perugia
Netherlands Academisch Ziekenhuis Maastricht Maastricht
United Kingdom Hammersmith Hospital London
United States Ohio State University, Comprehesive Cancer Center Columbus Ohio

Sponsors (1)

Lead Sponsor Collaborator
Kiadis Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Italy,  Netherlands,  United Kingdom, 

References & Publications (2)

Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. — View Citation

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. Review. — View Citation

Outcome

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