CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL

NCT04303247 | Unknown Early Phase 1

• 1 other identifier: dual CD19/CD22 CAR-T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies. There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. To make further improvement, combining CD19 and CD22 as dual-targets for CAR-T cells, which adapt the FasT CAR-T cells manufacture technology to shorten the manufacture time and maintain the stemness of CAR-T cells. We launch such a clinical trial using CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B-cell NHL to evaluate the efficacy and safety of CD19 and CD22 targeted CAR-T cell therapy.

Conditions

B-cell Lymphoma Refractory; B-cell Lymphoma Recurrent

Outcome Measures

Primary Outcomes (2)

• The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells

  ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

  4 weeks after infusion

• The safey evaluation of CD19 and CD22 targeted CAR-T cells

  the appearence of dosage limited toxicity

  within 4 weeks after infusion

Secondary Outcomes (1)

• The long-term efficiency of CD19 and CD22 targeted CAR-T cells

  up to 2 years after infusion

Study Arms (1)

CD19+CD22 targeted CAR-T

EXPERIMENTAL

The study will employ dose level cohorts of three patients that will be treated at each level described below, based on the number of T cells to be infused using the "3 + 3" dose-escalation strategy to find MTD followed by a dose-expansion phase at determined optimal dosage. dosage: the number of anti CD19+CD22 CAR T cells -1(if needed) 1×10\^5/KG 1. 3×10\^5 /KG 2. 6×10\^5 /KG 3. 1×10\^6/KG Treatment follows a lymphodepletion, chemotherapy regimen that consists of Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) for 3 days prior to cell infusion.

Biological: CD19 and CD22 targeted CAR-T cells

Interventions

CD19 and CD22 targeted CAR-T cells BIOLOGICAL

The T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma.

CD19+CD22 targeted CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a） Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
• Male or female subjects between the ages of 18 and 75（including critical values）；
• Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
• Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
• Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved complete remission after standard systematic treatment and second-line treatment. Or the disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell transplantation (not limited to the previous therapeutic regimen) ；
• Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline；
• Subjects with TFL must receive chemotherapy before transformation and meet the above definition of relapse or refractory after transformation.
• According to Lugano response criteria 2014, there should be at least one evaluable tumor focus: the longest diameter of intranodal focus \> 1.5cm, the longest diameter of extranodal focus \> 1.0cm；
• Positive expression of CD19 or CD22 in tumor tissue；
• Subjects who have no effect or relapse after single-target CAR-T treatment can also be included in the group.
• Approved anti-tumor therapies, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 2 weeks before the precondition.
• ECOG≤1；
• Life expectancy ≥ 3 months；
• Neutrophil absolute count ≥ 1×10\^9/L；
• platelet count ≥ 50×10\^9/L；

You may not qualify if:

• Any of the following points shall be deemed as no entry into this study：
• Other tumors except cured non-melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with complete remission of more than 5 years)；
• Severe mental disorders；
• A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
• History of allogeneic stem cell transplantation；
• Heart disease with grade III-IV heart failure \[NYHA classification\], myocardial infarction, angioplasty or stenting, unstable angina or other heart diseases with prominent clinical symptoms within one year before admission；
• Subjects with any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, bile drainage tube or pleura/peritoneum/pericardium catheter), should be excluded. (Special central venous catheter is allowed)；
• Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
• Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
• Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
• Active infection requiring systematic treatment within 2 weeks before single collection；
• Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
• History of autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic lupus erythematosus) that cause end-organ damage or require systemic immunosuppressive medications or systemic disease modifying drugs in the past 2 years；
• Presence of pulmonary fibrosis；
• Subjects who have received other clinical trial treatment within 4 weeks before participating in this trial should be excluded. Or the signing date of informed consent is within 5 half-lives of the last application of another clinical trial (whichever is longer)；

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator
• 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China: collaborator
• The Affiliated Hospital Of Guizhou Medical University: collaborator
• Tang-Du Hospital: collaborator
• The General Hospital of Western Theater Command: collaborator
• Chongqing University Cancer Hospital: collaborator

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

Location

MeSH Terms

Interventions

Antigens, CD19

Intervention Hierarchy (Ancestors)

Antigens, CD; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Antigens, Differentiation, B-Lymphocyte; Minor Histocompatibility Antigens; Histocompatibility Antigens; Isoantigens; Biomarkers

Study Officials

• Xi Zhang, MD phD

  Xinqiao Hospital of Chongqing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xi Zhang, MD phD

CONTACT

13808310064; zhangxxi@sina.com

Ruihao Huang

CONTACT

18984398751; 1169731117@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: no masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chef of Hematology Department

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 11, 2020
• Study Start: May 1, 2020
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2023
• Last Updated: March 11, 2020

Record last verified: 2020-03

Locations

CN (1)