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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma
ClinicalTrials.gov Identifier:
NCT00967343
First received: August 26, 2009
Last updated: March 22, 2013
Last verified: March 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Kiadis Pharma:

Primary Outcome Measures:
  • Transplant related mortality [ Time Frame: 6 and 12 months after the transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of acute and chronic graft-versus-host disease [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: Yes ]
  • Progression free survival [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: No ]
  • Incidence and severity of bacterial, viral or fungal infection [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: No ]
  • Health status (including Quality of Life) [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 24 months after the transplantation ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: August 2009
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATIR Biological: Donor lymphocyte preparation depleted of host functional alloreactive T-cells
Single intravenous infusion with 2x10E6 T-cells/kg

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967343

Locations
United States, Ohio
Ohio State University, Comprehesive Cancer Center
Columbus, Ohio, United States, 43210
Belgium
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
Germany
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
Italy
Perugia University
Perugia, Italy, 06123
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6229 HX
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 ONN
Sponsors and Collaborators
Kiadis Pharma
Investigators
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
  More Information

No publications provided

Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT00967343     History of Changes
Other Study ID Numbers: CR-AIR-004, EudraCT no. 2008-008198-73
Study First Received: August 26, 2009
Last Updated: March 22, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Germany: Paul-Ehrlich-Institut
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft-versus-host disease
Immune reconstitution
Alloreactive T-cells
Photodepletion
TH9402
Transplant related mortality
Hematologic malignancy

Additional relevant MeSH terms:
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 18, 2014