Acute Lymphoblastic LeukemiaPhase 1NCT03298828
CD19 CAR and PD-1 Knockout Engineered T Cells for CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma
A Phase 1 study testing CD19 CAR and PD-1 knock out engineered T-cells and CD19 CAR T-cells in people with Acute Lymphoblastic Leukemia and Burkitt Lymphoma, run by Third Military Medical University.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Burkitt Lymphoma
- What is being tested?
- CD19 CAR and PD-1 knock out engineered T-cells and CD19 CAR T-cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2017to Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1.Children and adults (age 70 years or younger) with high risk/relapsed CD19+ haematological malignancy:
- Resistant disease (>25% blasts) at end of UKALL 2011 or equivalent induction
- 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)
- 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)
- Intermediate risk infant ALL with MRD > 10-3 at end of Interfant06 induction
- Very early (< 18 months from diagnosis) bone marrow or extramedullary relapse of acute lymphoblastic leukaemia (ALL)
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- 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
- Any on therapy relapse of ALL in patients age 16-70
- Any relapse of infant ALL
- ALL post ≥ 2nd relapse
- Any refractory relapse of ALL
- ALL with MRD >10-4 prior to planned stem cell transplant
- Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
- Any relapse of ALL after stem cell transplant
- 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
Who cannot join
- CD19 negative disease
- Active hepatitis B, C or HIV infection
- Oxygen saturation ≤ 90% on air
- Bilirubin > 3 x upper limit of normal
- Creatinine > 3 x upper limit of normal
- Women who are pregnant or lactating
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- Stem Cell Transplant patients only: active acute graft-versus-host disease (GVHD) overall Grade ≥ II (Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring systemic steroids
- Inability to tolerate leucapheresis
- Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≤ 50%
- Severe intercurrent infection at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
- Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
- Allogeneic transplant recipients with active acute GVHD overall grade >2 or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
Trial locations and contacts
No sites are listed yet.
About this study
Official title: CD19 Chimeric Antigen Receptor (CAR) and PD-1 Knockout Engineered T Cells for CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma
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.
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia, Burkitt Lymphoma
- Being tested
- CD19 CAR and PD-1 knock out engineered T-cells, CD19 CAR T-cells
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 CAR and PD-1 knock out engineered T-cellsBiological
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.
CD19 CAR T-cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| CD19 CAR | Experimental | Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR T-cells. Receives: Biological: CD19 CAR T-cells |
| CD19 CAR and PD-1 knock out | Experimental | Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR and PD-1 knock out engineered T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR and PD-1 knock out engineered T-cells. Receives: Biological: CD19 CAR and PD-1 knock out engineered T-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular remission
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.
Measured: 1 month
Secondary outcomes (5)
Long term molecular remission
Number of patients in molecular remission without further therapy at 2 years
Measured: 2 years
Frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells
Persistence and frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells in the peripheral blood by flow cytometry and qPCR analyses.
Measured: 2 years
Incidence of hypogammaglobulinaemia
Incidence and duration of hypogammaglobulinaemia.
Measured: 2 years
Relapse rate
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).
Measured: 10 years
Overall Survival
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).
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2017
- Study startNov 2017 (estimated)
- Primary completionOct 2020 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Third Military Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaoyun Shang, Third Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03298828
- Sponsor's protocol ID
- TMMU-CAR-001
- Status last verified
- Sep 2017
- First submitted
- 24 Jul 2017
- Last updated
- 2 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD19 Chimeric Antigen Receptor (CAR) and PD-1 Knockout Engineered T Cells for CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma
- ClinicalTrials.gov ID
- NCT03298828
- Acronym / sponsor ID
- TMMU-CAR-001
- Conditions
- Acute Lymphoblastic Leukemia, Burkitt Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Third Military Medical UniversityUniversity, hospital or other
- Study start
- Nov 2017 (estimated)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 2 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD19 CAR | Experimental | Biological: CD19 CAR T-cellsPatients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR T-cells. |
| CD19 CAR and PD-1 knock out | Experimental | Biological: CD19 CAR and PD-1 knock out engineered T-cellsPatients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR and PD-1 knock out engineered T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR and PD-1 knock out engineered T-cells. |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- 1.Children and adults (age 70 years or younger) with high risk/relapsed CD19+ haematological malignancy:
- 2.Agreement to have a pregnancy test, use adequate contraception (if applicable)
- 3.Written informed consent
Key exclusion criteria (12 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD19 CAR and PD-1 knock out engineered T-cellsA 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. | Biological | CD19 CAR and PD-1 knock out |
| CD19 CAR T-cellsA 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. | Biological | CD19 CAR |
Primary outcome
Molecular remission
Time frame: 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.
5 secondary outcomes
Long term molecular remission
Time frame: 2 years
Frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells
Time frame: 2 years
Incidence of hypogammaglobulinaemia
Time frame: 2 years
Relapse rate
Time frame: 10 years
Overall Survival
Time frame: 10 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19 CAR and PD-1 knock out engineered T-cells and CD19 CAR T-cells in people with Acute Lymphoblastic Leukemia and Burkitt Lymphoma, run by Third Military Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaoyun Shang, Dr. (+8618580607020, shangxiaoyun@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Molecular remission (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2017.