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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

Primary Purpose

Myeloid Leukemia, Lymphoblastic Leukemia, Lymphoma

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Donor lymphocyte preparation depleted of host functional alloreactive T-cells

About this trial

This is an interventional prevention trial for Myeloid Leukemia focused on measuring Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATIR

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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).

Progression Free Survival

Incidence and Severity of Bacterial, Viral or Fungal Infection

Immune Reconstitution

Health Status (Including Quality of Life)

Overall Survival

Full Information

NCT ID

NCT00967343

First Posted

August 26, 2009

Last Updated

May 19, 2021

Sponsor

Kiadis Pharma

1. Study Identification

Unique Protocol Identification Number

NCT00967343

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Terminated

Study Start Date

August 2009 (undefined)

Primary Completion Date

February 2012 (Actual)

Study Completion Date

February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kiadis Pharma

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ATIR

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Donor lymphocyte preparation depleted of host functional alloreactive T-cells

Intervention Description

Single intravenous infusion with 2x10E6 T-cells/kg

Primary Outcome Measure Information:

Title

Transplant Related Mortality

Description

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)

Time Frame

6, 12 and 24 months after the transplantation

Secondary Outcome Measure Information:

Title

Incidence and Severity Graft-versus-host Disease (GVHD)

Description

GVHD was graded according to standard criteria as referred to in the reference module (Filipovich et al. 2005; Przepiorka et al. 1995).

Time Frame