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CD19-redirected Autologous Cells (CAR-CD19 T Cells)

Primary Purpose

CD19 Positive Malignant B-cell Leukemia and Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR-CD19 T cells

Fludarabine

Cyclophosphamide

About this trial

This is an interventional treatment trial for CD19 Positive Malignant B-cell Leukemia and Lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with documented CD19-positive malignant B cell leukemia and lymphoma.
1. Patients aged between 18 ~ 65 with malignant B cell leukemia and lymphoma.
2. CD19-positive B cell leukemia or lymphoma.
3. Expected survival > 12 weeks.
4. ECOG scores 0-1, or KPS scores > 80.
5. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
6. WBC ≥ 2.5×109/L; LY ≥ 0.7×109/L; LY% ≥ 15%.
7. Creatinine ≤ 2.0 mg/dL (176.8 μmol/L).
8. ALT/AST ≤ 2.5 ULN.
9. Bilirubin ≤ 2.0 mg/dL (34.2 μmol/L).
10. Prothrombin Time (PT) : International Normalized Ratio (INR) < 1.7, or PT is at most 4 s longer than normal value.

All tests results should comply with the above criteria. No continuing supportive care is received.

Exclusion Criteria:

1. CD19-negative B cell leukemia or lymphoma. 2. Feasibility assessment during screening demonstrates < 5% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to αCD3/CD28 costimulation.
3. Pregnant or lactating women. (The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.) 4. Active hepatitis B or hepatitis C infection. 5. HIV/AIDS infection. 6. Uncontrolled active infection. 7. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
8. Previously treatment with any gene therapy products. 9. Allergy to immunotherapy and associated drugs. 10. Patients with heart disease that is in need of treatment or with poorly controlled hypertension determined by investigators.
11. Patients with unstable or active ulceration or with gastrointestinal bleeding.
12. Patients with previous or planed organ transplantation. 13. Hyponatremia with concentration of sodium in the blood < 125 mmol/L. 14. Serum potassium (baseline) < 3.5 mmol/L (Patients can take potassium supplements to recover serum potassium level prior to participating the study).
15. Patients need anticoagulant (e.g. Warfarin or heparin). 16. Patients need long-term antiplatelet agent (Aspirin, dose > 300 mg/d; Clopidogrel, dose > 75 mg/d).
17. Any radiotherapy conducted within 4 weeks prior to blood sampling.

Sites / Locations

Renji Hospital, Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-CD19 T cells

Arm Description

Autologous T Cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day -9 - Day -4.

Outcomes

Primary Outcome Measures

Study related adverse events

Occurrence of study related adverse events, defined as NCI CTC ≥ Grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusional toxicity and any toxicity possibly related to the CAR-CD19 T cells.

Secondary Outcome Measures

Primary engraftment endpoint

Duration of in vivo survival of CAR-CD19 T cells is defined as "engraftment". The primary engraftment endpoint is the # DNA vector copies per mg blood of CAR-CD19 T cells on week 4 after the first infusion. Q-PCR for CAR-CD19 T vector sequences will also be performed after infusion at 24 hours, weekly x 4, monthly x 6, and every 3 months thereafter until any 2 sequential tests are negative documenting loss of CAR-CD19 T cells.

Anti-tumor responses

Describe anti-tumor responses to CAR-CD19 T cell infusions.

Overall survival

Describe overall survival and cause of death.

Full Information

NCT ID

NCT02933775

First Posted

October 13, 2016

Last Updated

October 13, 2016

Sponsor

RenJi Hospital

Collaborators

CARsgen Therapeutics Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02933775

Brief Title

CD19-redirected Autologous Cells (CAR-CD19 T Cells)

Official Title

Autologous T Cells With a Chimeric Antigen Receptor in Patients With CD19-positive Malignant B Cell Leukemia and Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Unknown status

Study Start Date

October 2016 (undefined)

Primary Completion Date

April 2018 (Anticipated)

Study Completion Date

January 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

RenJi Hospital

Collaborators

CARsgen Therapeutics Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is designed for determining the safety and relative engraftment levels of the redirected autologous T cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell leukemia and malignant lymphoma.

Detailed Description

A single arm open-label pilot study is designed to determine the safety, tolerability and engraftment potential of CAR-CD19 T cells in patients with CD19-positive malignant B cell leukemia and lymphoma. All subjects will receive CAR-CD19 T cells infusion. Primary objectives: Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 lentiviral vector (referred to as "CAR-CD19 T" cells). Determine the duration of in vivo survival of CAR-CD19 T cells. Secondary objectives: For patients with detectable disease, measure anti-tumor response due to CAR-CD19 T cells infusions. To determine the amplification and survival of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ as measured by the relative engraftment levels of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ cells over time. Estimate relative trafficking of CAR-CD19 T cells to tumors in bone marrow and lymphnodes. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CAR-CD19 T (loss of engraftment). Determine the relative subsets of CAR-CD19 T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

CD19 Positive Malignant B-cell Leukemia and Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-CD19 T cells

Arm Type

Experimental

Arm Description

Intervention Type

Genetic

Intervention Name(s)

CAR-CD19 T cells

Other Intervention Name(s)

CD19 Redirected Autologous Cells

Intervention Description

Initial dose: A total of 1 - 10×10^7 CAR-CD19 T cells/kg will be administered by 1 - 3 infusions. Subsequent dose will be based on the subject's response to initial dose.

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

30 mg/m^2/day×4 days

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

500 mg/m^2/day×2 days

Primary Outcome Measure Information:

Title

Study related adverse events

Description

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Primary engraftment endpoint

Description

Time Frame

2 years

Title

Anti-tumor responses

Description

Describe anti-tumor responses to CAR-CD19 T cell infusions.

Time Frame

2 years

Title

Overall survival

Description

Describe overall survival and cause of death.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with documented CD19-positive malignant B cell leukemia and lymphoma. Patients aged between 18 ~ 65 with malignant B cell leukemia and lymphoma. CD19-positive B cell leukemia or lymphoma. Expected survival > 12 weeks. ECOG scores 0-1, or KPS scores > 80. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis. WBC ≥ 2.5×109/L; LY ≥ 0.7×109/L; LY% ≥ 15%. Creatinine ≤ 2.0 mg/dL (176.8 μmol/L). ALT/AST ≤ 2.5 ULN. Bilirubin ≤ 2.0 mg/dL (34.2 μmol/L). Prothrombin Time (PT) : International Normalized Ratio (INR) < 1.7, or PT is at most 4 s longer than normal value. All tests results should comply with the above criteria. No continuing supportive care is received. Exclusion Criteria: 1. CD19-negative B cell leukemia or lymphoma. 2. Feasibility assessment during screening demonstrates < 5% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to αCD3/CD28 costimulation. 3. Pregnant or lactating women. (The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.) 4. Active hepatitis B or hepatitis C infection. 5. HIV/AIDS infection. 6. Uncontrolled active infection. 7. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. 8. Previously treatment with any gene therapy products. 9. Allergy to immunotherapy and associated drugs. 10. Patients with heart disease that is in need of treatment or with poorly controlled hypertension determined by investigators. 11. Patients with unstable or active ulceration or with gastrointestinal bleeding. 12. Patients with previous or planed organ transplantation. 13. Hyponatremia with concentration of sodium in the blood < 125 mmol/L. 14. Serum potassium (baseline) < 3.5 mmol/L (Patients can take potassium supplements to recover serum potassium level prior to participating the study). 15. Patients need anticoagulant (e.g. Warfarin or heparin). 16. Patients need long-term antiplatelet agent (Aspirin, dose > 300 mg/d; Clopidogrel, dose > 75 mg/d). 17. Any radiotherapy conducted within 4 weeks prior to blood sampling.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Honghui Huang, MD

honghui_huang@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fangyuan Chen, MD

Organizational Affiliation

RenJi Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Renji Hospital, Shanghai Jiaotong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200127

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Honghui Huang, MD

honghui_huang@163.com

First Name & Middle Initial & Last Name & Degree

Fangyuan Chen, MD

First Name & Middle Initial & Last Name & Degree

Honghui Huang, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

34515338

Citation

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Results Reference

derived

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CD19-redirected Autologous Cells (CAR-CD19 T Cells)

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