Clinical Trial to Evaluate CD19 CAR T (CT032) in Patients With Relapsed and/or Refractory Non-Hodgkin's B Cell Lymphoma

NCT03994913 | Completed Phase 1 DMC

• 1 other identifier: CT032-NHL-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, single arm study to evaluate the safety and tolerability of treatment with CT032 CAR-CD19 T in patients with relapsed and/or refractory non-Hodgkin's B cell lymphoma (R/R B-NHL).

Conditions

Refractory B-Cell Non-Hodgkin Lymphoma; Relapsed B-cell Non-Hodgkin Lymphoma

Keywords

Relapsed and/or Refractory B-cell Non-Hodgkin Lymphoma; CAR T

Outcome Measures

Primary Outcomes (8)

• Phase Ⅰ, Safety/Tolerability: Dose-limiting toxicity (DLT)

  Dose-limiting toxicity (DLT)

  28 days post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD)

  28 days post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)

  Incidence and severity of Treatment emergent adverse events (TEAE)

  28 days post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE

  Incidence and severity of AE related to study treatment

  through 2 months post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of AEs of special interest (cytokine release syndrome [CRS], CART-cell-related encephalopathy syndrome [CRES])

  Incidence and severity of AEs of special interest (cytokine release syndrome \[CRS\], CART-cell-related encephalopathy syndrome \[CRES\])

  through 2 months post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment

  Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment

  28 days after infusion

• Phase Ⅰ, Safety/Tolerability: Recommended Phase II Dose (RP2D)

  Recommended Phase II Dose (RP2D)

  through 2 months post administration of CAR-T cells

• Phase Ⅱ, Efficacy: Overall Remission Rate (ORR)

  Overall Remission Rate (ORR) (Partial remission and complete remission rate after infusion of CT032 CAR-CD19 T cells)

  through 6 months post administration of CAR-T cells

Secondary Outcomes (15)

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)

  through 24 months post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE

  through 24 months post administration of CAR-T cells

• Phase Ⅰ, Safety/Tolerability: Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method

  through 24 months post administration of CAR-T-cells

• Phase Ⅰ: the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method

  through 24 months post administration of CAR-T cells

• Phase Ⅰ, Efficacy: Overall Remission Rate (ORR)

  through 24 months post administration of CAR-T cells

Study Arms (1)

CAR-CD19-T Cells

EXPERIMENTAL

The subjects are enrolled into 3 dose levels cohorts in sequence.

Biological: CAR-CD19 T Cells

Interventions

CAR-CD19 T Cells BIOLOGICAL

The CAR- CD19 T cells (study drug) used in this study are chimeric antigen receptor specifically expressing T cells targeting CD19. Fludarabine and Cyclophosphamide are used for lymphodepletion.

CAR-CD19-T Cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject should participate in the clinical trial voluntarily, be fully aware of and informed of this study and sign informed consent (ICF), and be willing to follow and be able to complete all trial procedures;
• Age 18-70 years old, male or female;
• CD 19 positive, Relapsed and/or Refractory Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma after the transformation of Relapsed and/or Refractory DLBCL subjects by histopathological and/or cytology diagnosis; At least received second-line systemic anticancer treatments containing rituximab (or other anti-CD20 drugs) and anthracene (including autologous hematopoietic stem cell transplantation) , and had progressive disease (PD) or relapse after the latest treatment.
• The Eastern Cooperative Oncology Group (ECOG) score is 0 or 1 point;
• The expected survival period is more than 12 weeks;
• Having sufficient venous pathways (for leukapheresis or intravenous blood collection) and no leukapheresis contraindications;
• At least one measurable lesion: the long axis \>1.5 cm of the lymph node lesion, or the long axis \>1.0 cm of the non-lymph node lesion;
• subject has adequate organ function at screening;
• Women of childbearing age must undergo a serum pregnancy test with negative results before screening and lymphodepletion preconditioning with fludarabine and cyclophosphamide, and are willing to use effective and reliable method of contraception for at least 1 year after T cell infusion;
• Male subjects who have an active sex life with a woman with reproductive potential must be willing to use very effective and reliable methods of contraception for at least 1 year after T cell infusion.

You may not qualify if:

• If the subject meets any of the following criteria, he or she cannot participate in this trial:
• A history of severe allergies, or a history of allergies or intolerance to fludarabine, cyclophosphamide or tocilizumab, or a history of allergies or intolerance to CAR T cell cytosolic component, or a history of allergic to beta-caprolactam antibiotics;
• Received chemotherapy, targeted therapy, radiotherapy and other anti-tumor treatment within 14 days before peripheral blood mononuclear cells (PBMCs) collection;
• Previously received any target of CAR T treatment, or previously received CD19 targeted drug treatment;
• Has undergone allogeneic hematopoietic stem cell transplantation; autologous stem cell transplantation was received within 12 weeks before PBMCs collection;
• Other malignant neoplasms existed in the previous 5 years or at the same time, with the exception of breast/cervical in situ cancer, cured basal cell carcinoma and superficial bladder tumor (Ta, Tis, T1);
• Any uncontrollable active infection, including but not limited to active TB patients
• subjects who had received a therapeutic dose of systemic steroid drugs (prednisone \>20mg/days or equivalent doses of other hormones) or other immunosuppressants within 7 days before PBMCs collection, with the exception of those who had recently or currently used inhaled steroids;
• Known to have active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, etc., that need long-term immunosuppressive therapy;
• Patients with refractory hyponatremia and/or hypokalemia;
• Known or existing primary or metastatic central nervous system lymphoma, or any other central neurological disease or clinically significant neurological examination with abnormal results (such as seizures, cerebrovascular ischemia/hemorrhage, dementia, etc.);
• Within 6 months prior to signing the ICF, there were any of the uncontrolled cardiovascular, cerebral vascular disease, diabetes and pulmonary embolism, or other disease at discretion of investigators that participating in this clinical trial may harm the health of the subjects;
• Oxygen absorption before PBMCs collection to maintain blood oxygen saturation \>95% (finger vein oxygen);
• According to the investigator, any serious or uncontrollable systemic disease, systematic comorbidities, other serious concurrent diseases (such as hemophagocytic syndrome, etc.), special circumstances of the tumor may make the subjects inappropriate to enter the study or non-compliant to the protocol, or produce significant interference to correct evaluation of study drug safety, toxicity, and validity;
• The investigators assessed that the subjects were unable or unwilling to comply with the requirements of the research protocol;

Sponsors & Collaborators

• CARsgen Therapeutics Co., Ltd.: lead
• First Affiliated Hospital of Zhejiang University: collaborator
• RenJi Hospital: collaborator

Study Sites (2)

Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jie Jin, Dr.

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 21, 2019
• Study Start: August 14, 2019
• Primary Completion: January 20, 2021
• Study Completion: May 27, 2021
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)