Hematological and non-hematological malignancies, and non-malignant diseases, requiring allogeneic blood stem cell transplantation without available HLA-identical donor. MedDRA version: 18.1 Level: PT Classification code 10063581 Term: Stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: TCRabCD19PBSC
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Mobilized peripheral blood stem cells from allogeneic donors depleted of
Sponsors
Miltenyi Biotec GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adult and paediatric patients with hematological malignancies in complete remission (CR), partial remission (PR) or with stable disease - Acute myeloid leukemia (AML): Patients with high-risk AML in CR1 Patients with relapsed or primary therapy-refractory AML - Acute lymphoid leukemia (ALL): Patients with high-risk ALL in CR1 Patients with relapsed or primary refractory ALL - Hodgkin’s disease: Patients with relapsed or primary refractory Hodgkin’s disease - Non-Hodgkin’s lymphoma: Patients with relapsed or primary refractory Non-Hodgkin’s lymphoma - Myelodysplastic Syndrome (MDS)/ Myeloproliferative Syndrome (MPS): Patients with refractory MDS/MPS - Multiple myeloma (MM): Patients with relapsed or refractory multiple myeloma • Adult and paediatric patients with non-hematological malignancies without curative treatment option, mainly - Neuroblastoma: Patients with relapsed metastatic nmyc-negative or -positive or local nmyc-positive neuroblastoma - Soft tissue sarcoma: relapsed metastatic soft tissue sarcoma (rhabdomyosarcoma, Ewing sarcoma, peripheral neuroectodermal tumor) soft tissue sarcoma with primary bone metastases or bone involvement in patients older than 10 years • Adult and paediatric patients with the following non-malignant diseases with HSCT as curative treatment option Hematologic diseases, acquired and congenital Severe aplastic anemia (patients not responding to immune suppression) Paroxysmal nocturnal haemoglobinuria (PNH) Haemaphagocytic lymphohistiocytosis (HLH) Congenital immunodeficiencies Severe combined immune deficiency (SCID) and related diseases Chediak Higashi syndrome Congenital metabolic disorders Malignant osteopetrosis Lysosomal storage disorders (mucopolysacharidoses, leukodystrophies, glycoprotein disorders) Additional patient inclusion criteria: • No HLA-identical stem cell donor available as determined by high-resolution typing (maximum of 1 antigen or allelic mismatch are acceptable [9/10 match]), but eligible haploidentical donor with >1 antigenic or allelic mismatch (9/10-match) identified and at call; Exception: Haploidentical HSCT is medically indicated even if an HLA-identical donor is available and decision for haplo-identical HSCT has been made according to hospital routine prior to inclusion of the patient into this study. • Patients aged =8 weeks to =65 years • Male or female without childbearing potential or using medically adequate contraception • Karnofsky (patients >16 years)/Lansky (patients =16 years) index >60% • Patient in good clinical condition without concomitant diseases significantly increasing the risk of transplantation, see exclusion criteria • Adult patients without active infections at the time of transplantation • Pediatric patients without uncontrollable, progressive infections at the time of transplantation Are the trial subjects under 18? yes Number of su
Exclusion criteria
Exclusion criteria: Main exclusion criteria for patients: • Age >65 years or 2 mg/dL and elevation of transaminases higher than 400 U/L • Chronic active viral hepatitis • Adult patients: Ejection fraction grade II hypertension by CommonToxicity Criteria (CTC) • Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard • Respiratory failure necessitating supplemental oxygen • HIV infection • Female patients who are pregnant or breast feeding, or adults of reproductive potential not willing to use an effective method of birth control during study treatment and for at least 12 months thereafter. Note: Women of childbearing potential must have a negative serum pregnancy test at study entry. • Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study • Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction) • Patients unwilling or unable to comply with the protocol or unable to give informed consent • Treatment with any investigational product within 4 weeks prior to study treatment (transfusion of the IMP)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the safety/tolerability and feasibility of haploidentical PBSC grafts depleted of TCRa/ß+ and CD19+ cells using the CliniMACS TCRa/ß and CD19 Systems in adult and paediatric patients with hematological and non-hematological malignancies and specific non-malignant diseases, defined as the incidence of grade II–IV acute graft-versus-host disease (GVHD) on Day 100 post-transplantation.; Secondary Objective: Safety objectives • Incidence of grade I acute GVHD • Incidence and severity of chronic GVHD • Incidence of transplant-related mortality • Incidence and severity of acute infusional toxicity • Graft failure • Incidence and type of infections • Incidence, severity and type of adverse events, clinically relevant vital signs and safety laboratory parameters • Concomitant medication. Feasibility • Neutrophil and platelet engraftment • Overall survival • Disease free survival • Transfusion requirement • Incidence of relapse • Days of (re)hospitalization • Quality of Life Assessment Laboratory • Donor chimerism • Reconstitution of T, B, NK cell subsets • Reconstitution of Treg cells • Reconstitution of T Vbeta repertoire • Reconstitution of T gamma/delta repertoire • Thymic function • KIR genotyping of donor and recipient; reconstitution of NK-cell KIR repertoire • T cell activity • NK cell activity • Performance of the CliniMACS System ;Primary end point(s): Acute graft-versus-host disease grades II-IV;Timepoint(s) of evaluation of this end point: Day 100 post transplantation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence of grade I acute GVHD until Day 100 post-transplantation - Incidence and severity of chronic GVHD after 1 year and 2 years. - Incidence of Transplant-related mortality at all visits - Infusional toxicity: maximum toxicity on the day of transfusion evaluated by measuring vital signs prior to and at different times after transfusion.. - Primary graft failure: failure to achieve an absolute ANC >500/µl at Day +28 - Secondary graft failure: initial neutrophil engraftment followed by a decline in absolute neutrophil count (ANC) <500/µl and unresponsiveness to growth factor therapy - Recurrence or newly occurring infectious diseases at Day 100 and 1 year post-transplantation - Number of virus reactivations of CMV, ADV, EBV by PCR twice a week until Day 28, weekly until Day 70 and on Day 100 - Incidence, severity and type of adverse events up to day 100/serious adverse reactions from day 100 to 2 years - Vital signs and complete blood counts throughout the study - Laboratory values for clinical chemistry from Day –12 to Day 100 - Documentation of concomitant medication from Day 0 to Day 100 - Neutrophil and platelet engraftment from Day 0 to Day 28 - Overall survival at Day 100 and after 1 and 2 years - Disease-free survival at Day 100 and after 1 and 2 years - Transfusion requirement from Day 0 to Day 28 - Incidence of relapse at Day 100 and after 1 and 2 years - Number of days hospitalized after transplantation assessed at Day 28 and Day 100 - Quality of life at Day –12 (prior to conditioning), Day 100 and after 1 and 2 years Immune cell phenotyping of T, B and NK cell subsets on Days 7, 14, 21, 28, 63, 100 and month 6 and 12 | — |
Countries
Germany, Netherlands
Contacts
Public ContactClinical Trials Information
acromion GmbH
Outcome results
None listed