An open label, uncontrolled, multicentre, 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 atients receiving a CD34-selected peripheral blood stem cell graft from a related, halpoidentical donor.

Active, not recruiting

• Conditions: Patients with hematologic malignancies who are eligible for an allogeneic stem cell transplantation but without the availability of matched related or unrelated donor within 1 - 3 months of initiation of a donor search (to be detemined by the investigator); MedDRA version: 12.0Level: HLTClassification code 10028578Term: Myeloproliferative disorders (excl leukaemias); MedDRA version: 12.0Level: LLTClassification code 10009015Term: Chronic myeloid leukemia; MedDRA version: 12.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemia; MedDRA version: 12.0Level: LLTClassification code 10000886Term: Acute myeloid leukemia; MedDRA version: 12.0Level: LLTClassification code 10000887Term: Acute myeloid leukemia in remission; MedDRA version: 12.0Level: LLTClassification code 10028228Term: Multiple myeloma; MedDRA version: 12.0Level: LLTClassification code 10028233Term: Multiple myeloma without mention of remission; MedDRA version: 12.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrent; MedDRA version: 12.0Level: LLTClassification code 10066110Term: T-cell lymphoblastic leukemia acute

• Registration Number: EUCTR2008-008198-73-NL
• Lead Sponsor: Kiadis Pharma Netherlands B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Recipient Inclusion Criteria (any of the following)
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 emission.
• Acute Lymphoblastic Leukemia (ALL): ALL in first remission with high-risk features (presenting leukocyte count > 30,000/mm3, karyotypes t(9;22), t(11;19), and t(4;11) biphenotypic leukemia, pro-B-ALL, late CR after induction therapy, T-ALL, rising MRD markers). All ALL in second remission.
• Myelodysplastic Syndrome (MDS): Transfusion dependent MDS in IPSS risk group ‘int 1’ (0.5-1.0).
• Ph-positive chronic myeloid leukemia (CML): Patients with CML in first chronic phase (CP) who have failed (either resistant or intolerant) at least 2 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. 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 concurrently not featuring bulky disease (defined as lymphomas = 5 cm).
• Myelodysplastic Syndrome (MDS): MDS in IPSS risk group ‘int 2’ (score 1.5-2.0). MDS in IPSS risk group ‘high’ (score = 2.5). Patients with more than 20% blasts in the marrow will be considered AML.
• Chronic Myeloid Leukemia (CML): Patients with CML in second or later chronic phase. Patients with blast crisis will be considered AML. Patients with accelerated phase will be excluded.
• 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 requiring treatment (Binet C or A/B with active disease” according to the NCI criteria) and refractory to or progressive after a previous fludarabine- or equivalent purine-based regimen. These patients must at least achieve a partial remission. CLL transformed to high grade lymphoma (Richter transformation) will be excluded.
• Myeloproliferative Syndrome (MPS): Myeloproliferative disorders in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia. Patients with more than 20% blasts in the marrow will be considered AML.

Other Inclusion Criteria
• Male or female, age = 18, = 65 years.
• Ability to comprehend the investigational nature of the study and provide informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 ye

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 extramedullar disease or being non-responsive to prior therapy
• CML featuring concurrent accelerated phase or blast crisis
• CLL concurrently transformed into high-grade lymphoma
• NHL with concurrent bulky disease (>= 5 cm)
• DLCO < 40% predicted.
• Left ventricular ejection fraction < 40% (evaluated by ECHO 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified