Clinical Study of Targeting CD19 and CD22 Chimeric Antigen Receptor T Lymphocytes in the Treatment of Recurrent or Refractory B Cell Non-Hodgkin Lymphoma

Clinical Study of Targeting CD19 and CD22 Chimeric Antigen Receptor T Lymphocytes in the Treatment of Recurrent or Refractory B Cell Non-Hodgkin Lymphoma

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed and Refractory; Lymphoid Hematological Malignancies
• Intervention / Treatment: Drug: GC022F CAR-T cells

Detailed Description

This is a single-arm, single-center, open clinical study to evaluate the safety and efficacy of GC022F injection in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yongxian Hu, MD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 18-75 years old (including the threshold value);

2. Histologically confirmed as diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), or primary mediastinal B-cell lymphoma (PMBCL) :

   i. Refractory B-NHL: PD was the optimal response to standard first-line treatment (those with intolerance to first-line treatment were not included in this study); Or SD after at least 4 courses of first-line treatment, and the DURATION of SD shall not exceed 6 months after the last treatment; Or the subjects' best response to the last treatment of second-line or above treatment is PD, or SD after at least 2 courses of second-line or above treatment, and the SD maintenance time is not more than 6 months; Or:

   ii. Relapsed B-NHL: after standard systemic treatment and complete remission after second-line treatment, the disease recurred as certified by histopathology, or the recurrence as confirmed by histopathology within 1 year after autologous hematopoietic stem cell transplantation (not limited by previous treatment methods);

   iii. Patients with INVERt follicular lymphoma must receive chemotherapy prior to transformation and meet the above definition of recurrent or refractory after transformation;

3. according to Lugano treatment response standard (2014 version), there should be at least one evaluable tumor lesion: the longest diameter of the injunctional lesion was > 1.5cm, and the longest diameter of the injunctional lesion was b> 1.0cm;
4. Positive expression of CD19 and CD22 in biopsy sections of tumor tissues;
5. Patients who have failed or relapsed after single-target CAR-T therapy may also be enrolled.
6. Prior to the study, the approved anti-B-NHL treatment, such as systemic chemotherapy, general radiotherapy and immunotherapy, has been completed for at least 2 weeks;
7. ECOG≤1；
8. Expected survival ≥3 months;
9. Absolute count of neutrophils ≥ 1×109/L;
10. Platelet count ≥50×109/L;
11. Absolute lymphocyte count ≥1×108/L;

12. Adequate organ function reserve:

    1. ALANINE aminotransferase and aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
    2. Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
    3. Serum total bilirubin ≤1.5× UNL;
    4. The left ventricular ejection fraction (LVEF) of the subject was diagnosed by echocardiography ≥50%, and no clinically significant pericardial effusion was observed, and no clinically significant ecg abnormalities were observed;
    5. under natural indoor air environment, the basic oxygen saturation of > is 92%;
13. Vein access required for collection can be established, and there are no contraindications for leukocyte collection;
14. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion; male subjects with fertile partners must agree to use effective barrier contraceptive method at least one year after infusion and avoid sperm donation;
15. Voluntary signing of informed consent.

Exclusion Criteria:

1. Other tumors (except cured non melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast ductal carcinoma in situ, or other malignant tumors with complete remission for more than 5 years);
2. Persons with severe mental disorders;
3. A history of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome;
4. A history of allogeneic stem cell transplantation;
5. Heart disease with grade III-IV heart failure [New York Heart Association (NYHA) classification] or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically significant cardiac conditions within the year prior to enrollment;
6. The presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, bile drainage tube or pleural/peritoneal/pericardial catheter), allowing the use of a dedicated central venous catheter;
7. Subjects with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastasis;
8. A history or disease of the central nervous system, such as seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS;
9. The results of any of the following virology-ELISA tests were positive: HIV antibody, HCV antibody, TPPA, hepatitis B surface antigen;
10. There were active infections requiring systematic treatment within 2 weeks before single collection;
11. Persons with a known severe allergic reaction to cyclophosphamide or fludarabine, or with an allergic constitution;
12. A history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has caused injury to the terminal organs or requires systemic immunosuppressive/disease-modulating drugs within the past 2 years;
13. Pulmonary fibrosis is present;
14. Has received treatment in another clinical trial within 4 weeks prior to participation in this trial, or the date of signing of the informed consent is within 5 half-lives (whichever is longer) of the last medication used in the last other clinical trial;
15. Poor compliance due to physiological, family, social, geographical and other factors, unable to comply with the research program and follow-up plan;
16. The presence of a comorbiditie requiring systemic corticosteroid therapy (≥5 mg/ day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive agents within 6 months of study treatment was determined by the investigator;
17. Lactating women who do not want to stop breastfeeding;
18. Any other condition that the researcher considers inappropriate to be included in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of GC022F CAR-T cells; Each subject receive GC022F CAR T-cells by intravenous infusion	Drug: GC022F CAR-T cells; Each subject receive GC022F CAR-T cells by intravenous infusion; Other Names: GC022F CAR-T cells injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Proportion of patients with dose limiting toxicity (DLT) after cell infusion	Within 28 days after cell infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	24 months after cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate(ORR)	Assessment of ORR (ORR = CR + CRi ) at Month 1,3,6,12,18and 24	Month 1,3,6,12,18and 24
Progression-free survival (PFS)	Assessment of PFS at Month 6,12,18and 24	Month 6,12,18and 24
Overall survival (OS)	Assessment of OS at Month 6,12,18and 24	Month 6,12,18and 24
Duration of response(DOR)	Assessment of OS at Month 6,12,18and 24	Month 6,12,18and 24

Collaborators and Investigators

• Sponsor: He Huang
• Collaborators: Gracell Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 20, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 7, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 7, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: CAR-T cell therapy; CD19; CD22; lymphoid hematological malignancies
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Lymphoma; Neoplasms; Lymphoma, B-Cell; Hematologic Neoplasms; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: GC022F-ZhejiangU

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