Lymphoblastic T-Cell Lymphoma, T-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
CAR-T-based therapies, CD1a
Brief summary
First in humans, exploratory, open-label, single-arm, multicentre, non-competitive, dose escalation study to assess the safety and efficacy of CD1a-CAR T therapy in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL)
Interventions
BIOLOGICALCD1a-CAR T
Autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express CD1a chimeric antigen receptor administered by intravenous infusion following a dose-escalation approach
Sponsors
OneChain Immunotherapeutics
BioClever 2005 S.L.
Hospital Clinic of Barcelona
Hospital Sant Joan de Deu
Astrum CRO, S.L.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Children older than 2 years or adults, male and female in both groups. 2. Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed. 3. R/R CD1a-positive T-ALL/LL patients defined as: * Failure to achieve morphological complete remission (\> 5% bone marrow blasts) or persistence of extramedullary disease after at least two cycles of chemotherapy. * First or subsequent relapse, including morphologic or MRD-detectable (≥1x10-4 ) bone marrow and/or extramedullary relapses after at least one standard frontline therapy. * Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT). * Primary refractoriness, defined as either morphologic persistence or detectable MRD (≥1x10-4 ) after at least two cycles of chemotherapy, making the patient not candidate for allo-HSCT. 4. Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study.
Exclusion criteria
1. Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), \<45%), pulmonary, liver, renal or CNS dysfunction. 2. Allo-HSCT within a time frame \<3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD). 3. Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease. 4. Active bacterial, fungal or viral infection not controlled by adequate treatment. 5. Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection. 6. Women who are pregnant (urine/blood pregnancy test positive) or lactating. 7. Severe illness or medical condition, which would not permit the patient to be managed according to the protocol. 8. Suffering from a serious autoimmune disease or immunodeficiency disease. 9. The patient participated in other experimental drug clinical trial within 6 weeks prior to OC-1 infusion. 10. Other non-controlled concomitant neoplasms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events grade III-IV | 1 year particularly the first 28 days after infusion | Number of adverse events grade III-IV using common toxicity criteria (CTC) |
| Incidence of severe Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) | 1 year particularly the first 28 days after infusion | Incidence of severe Cytokine release syndrome (CRS) (≥ grade III) and Immune effector cell-associated neurotoxicity syndrome (ICANS) (≥ grade II) |
| Non-relapse treatment-related mortality (NRM) | 1 year | Non-relapse treatment-related mortality (NRM) |
| Number of adverse events of special interest (AESI) | 1 year | Number of adverse events of special interest (AESI) |
| Assessment of the immunological homeostasis | 1 year | Assessment of the immunological homeostasis, through the identification of lymphocytes subpopulations by flow cytometry at each study timepoint. |
| Incidence of the treatment-related dermatological events | 1 year | Incidence of the treatment-related dermatological events |
| Number of patients developing dose limiting toxicity (DLT) | first 28 days after infusion | Number of patients developing dose limiting toxicity (DLT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate | 1 year | Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment. |
| Response rates | 1 year | Percentage of patients presenting CR, CRi, morphologic leukaemia-free status (MLFS), and no remission (NR). In the presence of extramedullary disease, complete remission (CR), partial remission (PR), stable disease (SD), disease recurrence or progression (PD) shall be used to describe the response. |
| Complete remission duration (CRD) | 1 year | The time from the first documented date of complete remission until disease progression (in days) |
| Duration of remission | 1 year | The duration of the remission will be assessed from the first documented date of remission status until progression (in days) |
| Minimal residual disease (MRD) response | 1 year | Minimal residual disease (MRD) response by flow cytometry: blast count among patients presenting bone marrow complete response (sensitivity 10-4). |
| Progression-free survival (PFS) | 1 year | Time since the first OC-1 administration to the documented loss of response. |
| Overall survival | 1 year | Overall survival time since first OC-1 administration to date of death. |
| Persistence of OC-1 | 1 year | • Persistence of OC-1, as determined by flow cytometry and quantitative analysis by qPCR. Genomic copy number integrations of the CAR in peripheral blood (PB) T cells and percentage of CD1a CAR-expressing T cells. |
Countries
Spain
Contacts
CONTACTWilmar Castillo
CONTACTLaura Astier
Outcome results
None listed