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

A Clinical Study Evaluating the Safety and Efficacy of CAR-T19/CAR-T22 Treatment for Children With CD19 Positive Relapse or Refractory Childhood Acute Lymphoblastic Leukemia and Lymphoma

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yang Zhonghua; Phone Number: 18938688105; Email: zh.yang@bindebio.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Xiangya Hospital Central South University
      • Contact: Yang Minghua, PhD; Phone Number: 13973135843

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Biological: CAR-T19/CAR-T22; According to tumor burden and other conditions, patients will be treated with cyclophosphamide or fludarabine,then,CAR-T cells will be infused 48-72 hours later.The recommand dose is 1x10^5/kg-2.5x10^8/kg .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0	Safety evaluation	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-T cells testing	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.	60 months
Overall remission rate	Overall remission rate consists of complete remission rate and partial remission rate of patients being treated with CAR-T19/CAR-T22	60 months

Collaborators and Investigators

• Sponsor: Shenzhen BinDeBio Ltd.
• Collaborators: Xiangya Hospital of Central South University
• Investigators: Study Director: Yang Zhonghua, Shenzhen BinDeBio Tech Co.,Ltd

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 8, 2019
• Primary Completion (ANTICIPATED): October 30, 2021
• Study Completion (ANTICIPATED): October 8, 2024

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (ACTUAL): December 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: 2019XY-BDB011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No