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Myeloid LeukemiaPhase 2/3NCT00967343

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

A Phase 2/3 study testing Donor lymphocyte preparation depleted of host functional alloreactive T-cells in people with Myeloid Leukemia and Lymphoblastic Leukemia, run by Kiadis Pharma at 15 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Myeloid Leukemia, Lymphoblastic Leukemia, Lymphoma
What is being tested?
Donor lymphocyte preparation depleted of host functional alloreactive T-cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
15 sitesin 7 countries
Study dates
Aug 2009to Feb 2012
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • Myelodysplastic Syndrome (MDS)
  • Chronic Myeloid Leukemia (CML)
  • Multiple Myeloma (MM)
  • Chronic Lymphocytic Leukemia (CLL)
  • Myeloproliferative Syndrome (MPS)

Who cannot join

  • 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
Show all 33Show fewer
  • 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.

Trial locations and contacts

15 sites in 7 countries.

15 sites in 7 countries

Belgium4 sites

  • Algemeen Ziekenhuis Sint-Jan

    Bruges, 8000

  • Université Libre de Bruxelles - Institute Jules Bordet

    Brussels, 1000

  • Universitair Ziekenhuis Gasthuisberg

    Leuven, 3000

  • University of Liege - CHU Sart Tilman

    Liège, 4000

Other trials in Belgium

Germany4 sites

  • Universitätsklinikum Freiburg, Medizinische UNI-Klinik

    Freiburg im Breisgau, 79106

  • Universitätsklinikums Schleswig-Holstein Campus Kiel

    Kiel, 24105

  • Universitätsklinikum Mainz

    Mainz, 55101

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Canada3 sites

  • HHSC, Henderson Hospital Site

    Hamilton, Ontario, L8V 1C3

  • Maisonneuve-Rosemont Hospital

    Montreal, Quebec, H1T 2M4

  • Ontario Cancer Institute / Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

United States1 site

  • Ohio State University, Comprehesive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

Italy1 site

  • Perugia University

    Perugia, 06123

Other trials in Italy

Netherlands1 site

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6229 HX

Other trials in Netherlands

United Kingdom1 site

  • Hammersmith Hospital

    London, W12 ONN

Other trials in United Kingdom

About this study

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

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 .

Read the 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.

Being tested
Donor lymphocyte preparation depleted of host functional alloreactive T-cells
Keywords
Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy
Medical subject headings
Leukemia, Myeloid, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes, Myeloproliferative Disorders, Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor lymphocyte preparation depleted of host functional alloreactive T-cellsBiological

    Single intravenous infusion with 2x10E6 T-cells/kg

Study groups in NCT00967343
Study groupRoleWhat they receive
ATIRExperimentalNot described
Receives: Biological: Donor lymphocyte preparation depleted of host functional alloreactive T-cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 6, 12 and 24 months after the transplantation

Secondary outcomes (6)

  1. 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).

    Measured: Up to 24 months after the transplantation

  2. Progression Free Survival

    Measured: Up to 24 months after the transplantation

  3. Incidence and Severity of Bacterial, Viral or Fungal Infection

    Measured: Up to 24 months after the transplantation

  4. Immune Reconstitution

    Measured: Up to 24 months after the transplantation

  5. Health Status (Including Quality of Life)

    Measured: Up to 24 months after the transplantation

  6. Overall Survival

    Measured: 6, 12, and 24 months after the transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionFeb 2012
  4. Study completionFeb 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00967343
Sponsor's protocol ID
CR-AIR-004
Other IDs
EudraCT no. 2008-008198-73
Status last verified
May 2021
First submitted
26 Aug 2009
Last updated
14 Jun 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 16338616

  • 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.

    PubMed 7581076

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Donor lymphocyte preparation depleted of host functional alloreactive T-cells in people with Myeloid Leukemia and Lymphoblastic Leukemia, run by Kiadis Pharma at 15 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Belgium, Germany, Canada, United States, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant Related Mortality (time frame: 6, 12 and 24 months after the transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00967343, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.

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