CD19 CAR and PD-1 Knockout Engineered T Cells for CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

NCT ID: NCT03298828

Last Updated: 2017-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-30

Study Completion Date

2022-10-31

Brief Summary

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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

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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

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Acute Lymphoblastic Leukemia Burkitt Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CD19 CAR

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.

Group Type EXPERIMENTAL

CD19 CAR T-cells

Intervention Type BIOLOGICAL

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.

CD19 CAR and PD-1 knock out

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.

Group Type EXPERIMENTAL

CD19 CAR and PD-1 knock out engineered T-cells

Intervention Type BIOLOGICAL

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.

Interventions

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CD19 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.

Intervention Type BIOLOGICAL

CD19 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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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

1. CD19 negative disease
2. Active hepatitis B, C or HIV infection
3. Oxygen saturation ≤ 90% on air
4. Bilirubin \> 3 x upper limit of normal
5. Creatinine \> 3 x upper limit of normal
6. Women who are pregnant or lactating
7. 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
8. Inability to tolerate leucapheresis
9. Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%

1. Severe intercurrent infection at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
3. 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
Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Third Military Medical University

OTHER

Sponsor Role lead

Responsible Party

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Xiaoyun Shang

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Xiaoyun Shang, Dr.

Role: CONTACT

+8618580607020

Other Identifiers

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TMMU-CAR-001

Identifier Type: -

Identifier Source: org_study_id