Patients with hematologic malignancies who are eligible for an allogeneic stem cell transplantation but without the availability of an (according to the treating physician) suitable matched related or unrelated donor following a donor search. MedDRA version: 14.0 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: LLT Classification code 10066110 Term: T-cell
Conditions
Interventions
Product Name: ATIR
Product Code: ATIR
Pharmaceutical Form: Solution for infusion
Sponsors
Kiadis Pharma Netherlands B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must comply with the recipient inclusion and exclusion criteria mentioned below. These criteria must be assessed before patient apheresis. 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). • 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. Group 1: Primary Indications • 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 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 re
Exclusion criteria
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) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the effects of the administration of a donor lymphocyte preparation selectively depleted of host alloreactive T-cells (ATIR) to patients with hematologic malignancies on 6 months and 12 months TRM.;Secondary Objective: • To study the effects of ATIR on Overall Survival (OS). • To study the effects of ATIR on the incidence and severity of acute GvHD. • To study the effects of ATIR on the incidence and severity of chronic GvHD. • To study the effects of ATIR on Progression Free Survival (PFS). • To study the effects of ATIR on the incidence and severity of bacterial, viral or fungal infections. • To study the effects of ATIR on immune reconstitution. • To study the effects of ATIR on the health status of patients (including Quality of Life [QoL]).;Primary end point(s): Incidence of TRM at 6 months and 12 months after the transplantation. ;Timepoint(s) of evaluation of this end point: Incidence of TRM at 6 and 12 months after the transplantation. Time to TRM will be calculated from the date of receipt of the HSCT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Survival (OS). • Incidence and severity of acute and chronic GvHD. • Progression free survival (PFS). • The incidence, severity and duration of fungal, viral and bacterial infections occurring within the first year following HSCT. • Immune reconstitution. • To measure the health status of patients, the EQ-5D and the Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) will be used. ;Timepoint(s) of evaluation of this end point: Patients will be assessed weekly for the first 100 days after the transplant. Patients will be assessed every month up to 6 months after the transplantation, every 2 months up to 12 months after the transplantation and subsequently every 3 months up to 24 months after the transplantation. Patients will be followed-up for 24 months to assess overall survival. | — |
Countries
Belgium, Canada, France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactDirector Quality Assurance
PharmaCell BV
Outcome results
None listed