A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Diffuse Non-Hodgkin Lymphoma

NCT04232826 | Completed Phase 1

• 1 other identifier: HY-CD19 CART-002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory diffuse Non-Hodgkin lymphoma.

Conditions

Diffuse Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)

  Determine the MTD and DLT of CNCT19 in the Treatment and recommend the dose for Phase II study.

  28 days

• Safety of CNCT19 therapy: CTCAE v5.0

  Safety measures include adverse events as assessed by CTCAE v5.0.

  24 months

Secondary Outcomes (9)

• Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

  3 months

• Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

  28 days

• Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

  2 months

• Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

  6 months

• Best Overall Response (BOR)

  24 months

Study Arms (1)

Single dose of CNCT19

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.

Biological: single dose of CNCT19

Interventions

single dose of CNCT19 BIOLOGICAL

Dose A: 1.00 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide Dose B: 2.00 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide Dose C: 4.00 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

Single dose of CNCT19

Eligibility Criteria

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

You may qualify if:

• Informed consent is signed by the subject.
• Age 18 to 75.
• Relapsed or refractory NHL with CD19-positive after at least two systemic lines of therapy
• a. Diffuse large B cell lymphoma (DLBCL) non-specific (NOS), T-cell / Histiocyte Rich large B-cell lymphoma, elderly EBV-positive diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), chronic inflammation-associated DLBCL, follicular lymphoma (FL) transformed large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and / or BCL6 rearrangement and High-grade B-cell lymphoma-unspecified; b. Chemotherapy-refractory disease, defined as one of more of the following:
• No response to last line of therapy; i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to at least 4 courses of first-line treatment / at least 2 courses of end-line treatment (2 lines and above) with duration no longer than 6 month from last dose of therapy OR;
• Refractory post-autologous stem cell transplant (ASCT); i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals); ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy; Any BM relapse after autologous stem cell transplantation (ASCT); c. Individuals must have received two systemic lines of therapy
• anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative;
• an anthracycline containing chemotherapy regimen;
• FL-transformed DLBCL must have received pre-chemotherapy for FL and become resistant after conversion to DLBCL.
• At least one measurable lesion, defined as at least 1 lymph node \>1.5 cm in the longest diameter, per revised IWG Response Criteria.
• Any previous systemic immune checkpoint therapy (such as anti-PD1 / PD-L1 monoclonal antibody, etc.), at least 3 half-lives away from the Cell Product Preparation; other systemic treatments should be stoped at least 2 weeks or 5 half-lives before Cell Product Preparation (shorter Whichever comes first).
• Eastern cooperative oncology group (ECOG) performance status of 0 to 1.
• Sufficient bone marrow reserves defined as:
• Absolute neutrophil (ANC) \> 1,000 / mm3;
• Lymphocyte absolute value (ALC) ≥ 100 / mm3;

You may not qualify if:

• Active CNS involvement by malignancy.
• Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded:
• Lymphodepleting Chemotherapy prescribed by the protocol;
• CNS prophylaxis treatment must be stopped \> 1 week prior to CNCT19 infusion.
• Has had treatment with any prior anti-CD19 therapy.
• Plans to receive autologous stem cell transplantation (ASCT) within 6 weeks before the CNCT19 infusion.
• Patients who have previously received Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT).
• Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, systemic lupus erythematosus) and active or uncontrolled autoimmune disease (such as autoimmune hemolytic anemia, etc.).
• Patients who are positive for any of HBsAg, HCV-Ab, TP-Ab.
• Patients who have previously received surgery within 4 weeks before the screening that was unsuitable for enrollment by the investigator's assessment.
• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease. Patients with Prior malignancy that has been cured for ≥ 2 years are excluded.
• a. Left Ventricular Ejection Fraction (LVEF) ≤45%; b. III/IV congestive heart failure (NYHA); c. Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular tachycardia); d. QTc≥450ms (male)or QTc≥470ms (female)(QTcB=QT/RR1/2); e. Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery \< 6 months prior to CNCT19 infusion; f. Clinically significant valvular disease; g. Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.
• Clinically significant pleural effusion.
• Patients with a history of epilepsy, cerebrovascular ischemia / hemorrhage, cerebellar disease or other active central nervous system diseases.
• Lymphoma affects the atrium or ventricle.

Sponsors & Collaborators

• Juventas Cell Therapy Ltd.: lead

Study Sites (2)

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

Location

Study Officials

• Dehui Zou, Dr.

  Institute of Hematology & Blood Diseases Hospital, China

  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: January 11, 2020
• First Posted: January 18, 2020
• Study Start: January 15, 2020
• Primary Completion: January 1, 2021
• Study Completion: November 1, 2022
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

CN (2)