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.

Phase 2

Completed

Conditions: cancer of the blood and immune system
hematological malignancies
10018849

Registration Number: NL-OMON36698

Lead Sponsor: Kiadis Pharma Netherlands B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

Recipient Inclusion Criteria (any of the following)
Initially, both patients with primary and secondary indications are eligible for the trial. During the trial accrual may be limited to the primary indications based on a recommendation made by the Independent Data Monitoring Committee (IDMC). ;Group 1: Primary Indications
• Acute Myeloid Leukemia (AML): AML in first remission with high risk features (secondary AML, FLT-3 mutation, complex karyotype, abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), or other cytogenetic anomaly of similar poor prognosis, or need for 2 induction regimens to achieve a complete remission (CR)). All AML in second remission.
• Acute Lymphoblastic Leukemia (ALL): ALL in first remission with high-risk features (presenting leukocyte count > 30,000/mm3 for B-cell ALL or > 100,000/mm3 for T-cell ALL, karyotypes t(9;22), t(11;19), and t(4;11) biphenotypic leukemia, pro-B-ALL, late CR after induction therapy, rising MRD markers). All ALL in second remission.
• Myelodysplastic Syndrome (MDS): Transfusion-dependent MDS with low or intermediate-1 IPSS score, and all MDS with intermediate-2 or high IPSS score. Patients with more than 20% blasts in the marrow will be considered AML.
• Ph-positive chronic myeloid leukemia (CML): Patients with Ph-positive CML in first chronic phase (CP) who have failed (either resistant or intolerant) at least 2 tyrosine kinase inhibitors and any patient with the T315I mutation (irrespective of prior tyrosine kinase inhibitors).;Group 2: Secondary Indications
• AML:
- All AML not belonging to Group 1 in subsequent remission or with evidence of chemo-sensitive disease or,
- Patients requiring 3 or more induction regimens to achieve a first remission or,
- Patients with AML in hematologic remission who relapsed more than 2 years after allogeneic stem cell transplantation.
• ALL: All ALL not belonging to Group 1 in subsequent remission or with evidence of chemo-sensitive disease. Patients with ALL in hematologic remission who relapsed more than 2 years after allogeneic stem cell transplantation.
• Non-Hodgkin Lymphoma (NHL): All high grade and low grade Non-Hodgkin lymphoma (other than CLL and MM) in 2nd or 3rd remission (at least PR) after standard of care treatments including autologous stem cell transplantation.
• Chronic Myeloid Leukemia (CML): Patients with accelerated phase CML or CML in second or later chronic phase.
• Multiple Myeloma (MM): Secretory MM with or without osteolytic lesions concurrently not featuring extramedullary disease responsive to prior autologous stem cell transplantation(s) or at least one standard of care treatment (defined as 50% reduction of paraprotein in serum/plasma and/or 75% reduction of paraprotein in urine).
• Chronic Lymphocytic Leukemia (CLL):
- CLL non-responsive or early relapsed (within 12 months) after a previous fludarabine- or equivalent purine-based regimen or,
- CLL relapsed (within 24 months) after purine analogue combination therapy or treatment of similar efficacy (i.e. autologous stem cell transplantation) or,
- CLL with p53 deletion/mutation (i.e. del 17p-) requiring treatment.
• CLL transformed to high grade lymphoma (Richter transformation) having demonstrated at least PR.
• MPS: Myeloproliferative disorders in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia including atypical (Ph negative) chronic myeloid and neutrop

Exclusion Criteria

Recipient Exclusion Criteria (any of the following)
• AML in 1st CR with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21).
• MM featuring concurrent extramedullary 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 PR.
• NHL with concurrent bulky disease (>= 5 cm).
• Diffusing Capacity for Carbon Monoxide (DLCO) < 40% predicted.
• Left ventricular ejection fraction < 40% (evaluated by echocardiogram or MUGA).
• AST/SGOT > 2.5 x ULN (CTCAE grade II v3.0).
• Bilirubin > 1.5 x ULN (CTCAE grade II v3.0).
• Creatinine > 1.5 x ULN (CTCAE grade II v 3.0).
• HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation).
• Positive pregnancy test for women of childbearing age.
• Prior haploidentical PBSC 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* (e.g., dimethyl sulfoxide).
• Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study.;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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Incidence of TRM at 6 months and 12 months after the transplantation. All<br /><br>deaths during the trial will be assessed by the Central Endpoint Adjudication<br /><br>Committee (CEAC) to diferrentiate between TRM and death due to other causes.<br /><br>TRM is defined as death due to causes other than disease relapse or<br /><br>progression, or other causes which are unrelated to the transplant procedure<br /><br>(e.g. accident, suicide).</p><br>

Secondary Outcome Measures