A Clinical Study of CAR-T Cells Treatment for Children With CD19+/CD22+ R/R ALL and Lymphoma

Phase 1

Recruiting

• Conditions: Relapsed/Refractory B-cell Lymphoma, Childhood; Relapsed B-cell Acute Lymphoblastic Leukemia, Childhood; Refractory B-cell Acute Lymphoblastic Leukemia, Childhood
• Interventions: Biological: CAR-T19/CAR-T22

• Registration Number: NCT04204161
• Lead Sponsor: Shenzhen BinDeBio Ltd.

Brief Summary

This is a single arm, open-label, uni-center, phase I study . In this study, Children withCD19+/CD22+ R/R B-cell acute lymphoblastic leukemia or lymphoma will be treated with CAR-T19/CAR-T22 Immunotherapy to determine the safety and efficacy of treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-10-08
• Study First Submitted: 2019-12-13
• Study First Submitted QC: 2019-12-17
• Study First Posted: 2019-12-18
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-03
• Last Update Posted: 2021-02-04
• Primary Completion: 2021-10-30
• Study Completion: 2024-10-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Male and female subjects with CD19+/CD22+ B cell malignancies who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.

  1. no available curative treatment options (such as autologous or allogeneic SCT)
  2. If patients had receive immunotherapy, they should reach requirments:tumor recurrency or the number of B cells recovered.
  3. Patients with recurrence after hematopoietic stem cell transplantation need additional satisfaction: 1) no GvHD and not require immunosuppression;2) stem cell transplantation was completed for at least 4 months, and at least 6 months before the CART reinfusion;
  4. Patients must be willing to sign an informed consent.
  5. Age:≤18 years.
  6. survival>12 weeks
  7. Flow cytometry or IHC showed positive expression of CD19/ CD22 in tumor cells within two months.
  8. Routine blood test:hemoglobin>=90 g/L; platelet>=50×10^9/L.
  9. Liver function: ALT and AST≤2.5 (ULN) times the upper limits of normal (if abnormal liver function is mainly caused by tumor infiltration, it can ≤5 ULN), bilirubin <2.0 mg/dl.
  10. Renal function:BUN: 9-20mg / dl; serum creatinine<= 1.5 times upper limits of normal; endogenous creatinine clearance rate>=50 ml/min
  11. Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV.
  12. Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)>=55%.
  13. ECOG score ≤2。
  14. Adequate venous access for apheresis, and no other contraindications for leukapheresis

Exclusion Criteria

1. ECOG >= 3.
2. Patients with history of T cell tumors .
3. organ failure:heart failure Ⅲ and Ⅳ;The liver reached grade C of child-turcotte .Renal failure and uremia;Respiratory failure;People with impaired consciousness.
4. Acute or chronic GVHD after allogeneic hematopoiesis. Hormone or immunosuppressant was used within 30 days.
5. steroid hormoneswere used before and after blood collection and infusion.
6. HIV infection or active hepatitis B or hepatitis C infection.
7. Uncontrolled active infection.
8. Enrolled to other clinical study in the last 4 weeks.
9. Subjects with systemic auto-immune disease or immunodeficiency.
10. Allergic to cytokines.
11. Definite neuropathic or psychotic patients, including authors of dementia or seizures, history of psychotropic substance abuse and unable to quit, or other substantial lesions that may increase central neurotoxicity.
12. Patients with malignant tumors of the central nervous system.
13. Lung, brain or intestinal tumor infiltrates.
14. The second tumor was found.
15. Allergic to cytokine antagonists.
16. Other patients that researchers considered unsuitable for inclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T19/CAR-T22	CAR-T19/CAR-T22	CAR-T19/CAR-T22 (autologous T cells transduced with CD19 / 22 CAR-ζ/4-1BB vector) will be administered to children with R/R B cell Acute Lymphoblastic Leukemia (ALL) or Lymphoma as an IV infusion on days 0, 1 and 2 in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0	60 months	Safety evaluation

Secondary Outcome Measures

Name	Time	Method
Overall remission rate	60 months	Overall remission rate consists of complete remission rate and partial remission rate of patients being treated with CAR-T19/CAR-T22
CAR-T cells testing	60 months	The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival.

Trial Locations

Locations (1)

Xiangya Hospital Central South University; 🇨🇳 Changsha, Hunan, China