Acute Lymphoblastic Leukemia, Burkitt Lymphoma
Conditions
Brief summary
The purpose of this study is to evaluate the safety, efficacy and blood kinetics of autologous T cells genetically modified to express CD19 Chimeric Antigen Receptor and PD-1 knockout engineered T cells in patients with relapsed or refractory B-Cell Non-Hodgkin Lymphoma and Leukaemia.
Detailed description
This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD19 Chimeric Antigen Receptor (CAR) and PD-1 knock out engineered T-cells (CD19 CAR and PD-1 knock out engineered T-cells) in children and adults (age \<70 years) with high risk, relapsed CD19+ haematological malignancies (Acute Lymphoblastic Leukemia and Burkitt's lymphoma). Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19 CAR T-cells. Patients will receive the CD19 CAR and PD-1 knock out engineered T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR and PD-1 knock out engineered T-cells in children with high risk relapsed CD19+ malignancies.
Interventions
BIOLOGICALCD19 CAR and PD-1 knock out engineered T-cells
A single dose of 1 x 10\^6/kg CD19 CAR transduced and PD-1 knock out engineered T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.
BIOLOGICALCD19 CAR T-cells
A single dose of 1 x 10\^6/kg CD19 CAR transduced T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.
Sponsors
Third Military Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1.Children and adults (age 70 years or younger) with high risk/relapsed CD19+ haematological malignancy: 1. Resistant disease (\>25% blasts) at end of UKALL 2011 or equivalent induction 2. ALL with persistent high level MRD at 2nd time point of frontline national protocol (currently \> 5 x 10-3 at week 14 UKALL2011 or equivalent) 3. High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 109/L or poor steroid early response (i.e circulating blast count \>1x109/L following 7 day steroid pre- phase of Interfant 06) 4. Intermediate risk infant ALL with MRD \> 10-3 at end of Interfant06 induction 5. Very early (\< 18 months from diagnosis) bone marrow or extramedullary relapse of acute lymphoblastic leukaemia (ALL) 6. Early (within 6 months of finishing therapy) bone marrow, or combined extramedullary relapse of ALL with bone marrow minimal residual disease (MRD) \> 10-3 at end of re-induction 7. Any on therapy relapse of ALL in patients age 16-70 8. Any relapse of infant ALL 9. ALL post ≥ 2nd relapse 10. Any refractory relapse of ALL 11. ALL with MRD \>10-4 prior to planned stem cell transplant 12. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant 13. Any relapse of ALL after stem cell transplant 14. Any relapse of Burkitt's or other CD19+ lymphoma * 2.Agreement to have a pregnancy test, use adequate contraception (if applicable) * 3.Written informed consent
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular remission | 1 month | Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 1 month post CD19 CAR and PD-1 Knockout Engineered T-cell infusion will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of hypogammaglobulinaemia | 2 years | Incidence and duration of hypogammaglobulinaemia. |
| Long term molecular remission | 2 years | Number of patients in molecular remission without further therapy at 2 years |
| Frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells | 2 years | Persistence and frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells in the peripheral blood by flow cytometry and qPCR analyses. |
| Relapse rate | 10 years | Relapse rate monitored during interventional phase and long term follow up for a total of 10 years post cell infusion. Number of patients who relapsed can be summarized as a percentage (for all patients registered to the trial, and also only for those who received the cell infusion). |
| Overall Survival | 10 years | Overall survival is monitored during interventional phase and long term follow up for 10 years post-CD19 CAR and PD-1 Knockout Engineered T-cell infusion. Number of patients alive can be summarized as a percentage (for all patients registered to the trial, and also only for those who received the cell infusion). |
Contacts
Primary ContactXiaoyun Shang, Dr.
Outcome results
None listed