Clinical trial NCT02933775: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: CD19 Positive Malignant B-cell Leukemia and Lymphoma
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: CARsgen Therapeutics Co., Ltd.
First posted: 2016-10-14
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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:

1. 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).
2. Determine the duration of in vivo survival of CAR-CD19 T cells.

Secondary objectives:

1. For patients with detectable disease, measure anti-tumor response due to CAR-CD19 T cells infusions.
2. 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.
3. Estimate relative trafficking of CAR-CD19 T cells to tumors in bone marrow and lymphnodes.
4. 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).
5. Determine the relative subsets of CAR-CD19 T cells.

Eligibility criteria: 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.

Primary outcomes:
measure: Study related adverse events
timeFrame: 24 weeks
Secondary outcomes:
measure: Primary engraftment endpoint
timeFrame: 2 years
measure: Anti-tumor responses
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Fangyuan Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.