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

NCT ID: NCT00967343

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2012-02-29

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.

Conditions

Myeloid Leukemia; Lymphoblastic Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

ATIR

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of host functional alloreactive T-cells

Intervention Type: BIOLOGICAL

Single intravenous infusion with 2x10E6 T-cells/kg

Interventions

Donor lymphocyte preparation depleted of host functional alloreactive T-cells

Single intravenous infusion with 2x10E6 T-cells/kg

Intervention Type: BIOLOGICAL

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)

• 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.

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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kiadis Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephan Mielke, MD

Role: STUDY_CHAIR

Julius Maximilian University of Würzburg, Germany

Denis-Claude Roy, MD

Role: STUDY_CHAIR

Maisonneuve-Rosemont Hospital, Montreal, Canada

Andrea Velardi, MD

Role: PRINCIPAL_INVESTIGATOR

University Of Perugia

Katy Rezvani, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hammersmith Hospital, London, United Kingdom

Locations

Ohio State University, Comprehesive Cancer Center

Columbus, Ohio, United States

Algemeen Ziekenhuis Sint-Jan

Bruges, , Belgium

Université Libre de Bruxelles - Institute Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Gasthuisberg

Leuven, , Belgium

University of Liege - CHU Sart Tilman

Liège, , 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 im Breisgau, , Germany

Universitätsklinikums Schleswig-Holstein Campus Kiel

Kiel, , Germany

Universitätsklinikum Mainz

Mainz, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Perugia University

Perugia, , Italy

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Hammersmith Hospital

London, , United Kingdom

Countries

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

References

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. doi: 10.1016/j.bbmt.2005.09.004.

Reference Type: BACKGROUND

PMID: 16338616 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7581076 (View on PubMed)

Other Identifiers

EudraCT no. 2008-008198-73

Identifier Type: -

Identifier Source: secondary_id

CR-AIR-004

Identifier Type: -

Identifier Source: org_study_id