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Trial record 1 of 1 for:    NCT00967343
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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00967343
Recruitment Status : Terminated
First Posted : August 27, 2009
Last Update Posted : April 1, 2013
Information provided by (Responsible Party):
Kiadis Pharma

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 .

Condition or disease Intervention/treatment Phase
Myeloid Leukemia Lymphoblastic Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndrome Myeloproliferative Disorders Biological: Donor lymphocyte preparation depleted of host functional alloreactive T-cells Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : August 2009
Actual Primary Completion Date : February 2012
Actual Study Completion Date : February 2012

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

Primary Outcome Measures :
  1. Transplant related mortality [ Time Frame: 6 and 12 months after the transplantation ]

Secondary Outcome Measures :
  1. Incidence and severity of acute and chronic graft-versus-host disease [ Time Frame: Up to 24 months after the transplantation ]
  2. Progression free survival [ Time Frame: Up to 24 months after the transplantation ]
  3. Incidence and severity of bacterial, viral or fungal infection [ Time Frame: Up to 24 months after the transplantation ]
  4. Immune reconstitution [ Time Frame: Up to 24 months after the transplantation ]
  5. Health status (including Quality of Life) [ Time Frame: Up to 24 months after the transplantation ]
  6. Overall survival [ Time Frame: Up to 24 months after the transplantation ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00967343

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United States, Ohio
Ohio State University, Comprehesive Cancer Center
Columbus, Ohio, United States, 43210
Algemeen Ziekenhuis Sint-Jan
Brugge, Belgium, 8000
Université Libre de Bruxelles - Institute Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Gasthuisberg
Leuven, Belgium, 3000
University of Liege - CHU Sart Tilman
Liege, Belgium, 4000
Canada, Ontario
HHSC, Henderson Hospital Site
Hamilton, Ontario, Canada, L8V 1C3
Ontario Cancer Institute / Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Universitätsklinikum Freiburg, Medizinische UNI-Klinik
Freiburg, Germany, 79106
Universitätsklinikums Schleswig-Holstein Campus Kiel
Kiel, Germany, 24105
Universitätsklinikum Mainz
Mainz, Germany, 55101
Universitätsklinikum Würzburg
Würzburg, Germany, 97080
Perugia University
Perugia, Italy, 06123
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6229 HX
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 ONN
Sponsors and Collaborators
Kiadis Pharma
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Study Chair: Stephan Mielke, MD Julius Maximilian University of Würzburg, Germany
Study Chair: Denis-Claude Roy, MD Maisonneuve-Rosemont Hospital, Montreal, Canada
Principal Investigator: Andrea Velardi, MD University of Perugia, Italy
Principal Investigator: Katy Rezvani, MD PhD Hammersmith Hospital, London, United Kingdom

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Responsible Party: Kiadis Pharma Identifier: NCT00967343    
Other Study ID Numbers: CR-AIR-004
EudraCT no. 2008-008198-73
First Posted: August 27, 2009    Key Record Dates
Last Update Posted: April 1, 2013
Last Verified: March 2013
Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft-versus-host disease
Immune reconstitution
Alloreactive T-cells
Transplant related mortality
Hematologic malignancy
Additional relevant MeSH terms:
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Multiple Myeloma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases