Clinical Trials /

Phase II Clinical Trial of CNCT19 Cell Injection in the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT04586478

Description:

The study is a Phase II, single-arm, open-label, single-dose clinical trial, and its primary objective is to evaluate the efficacy and safety of CNCT19 Cell Injection in the treatment of relapsed or refractory NHL.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Clinical Trial of CNCT19 Cell Injection in the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
  • Official Title: Phase II Clinical Trial of CNCT19 Cell Injection in the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: HY001205
  • NCT ID: NCT04586478

Conditions

  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
single dose of CNCT19Single dose of CNCT19

Purpose

The study is a Phase II, single-arm, open-label, single-dose clinical trial, and its primary objective is to evaluate the efficacy and safety of CNCT19 Cell Injection in the treatment of relapsed or refractory NHL.

Detailed Description

      The study is a Phase II, single-arm, open-label, single-dose clinical trial, and its primary
      objective is to evaluate the efficacy and safety of CNCT19 Cell Injection in the treatment of
      relapsed or refractory NHL. The study consists of screening period (8 weeks), treatment
      period (4 weeks), and follow-up period (2 years at most).
    

Trial Arms

NameTypeDescriptionInterventions
Single dose of CNCT19ExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
  • single dose of CNCT19

Eligibility Criteria

        Inclusion Criteria:

          1. Patients who are willing to sign the informed consent form;

          2. Aged 18-75 years, male or female;

          3. At screening, subjects complying with the following diagnostic and treatment
             requirements:

               1. Complying with CD19-positive NHL according to the WHO classification 2017, which
                  are provided specifically as follows:

                    -  Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS);

                    -  Primary mediastinal large B cell lymphoma (PMBCL);

                    -  Transformed follicular lymphoma

                    -  High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and
                       high grade B cell lymphoma - not otherwise specified.

               2. Previously received≥2nd-line adequate therapy or autologous hematopoietic stem
                  cell transplantation (ASCT), including:

                    -  Received at least Rituximab or other CD20 targeted drugs containing (except
                       CD20 negative tumors) chemotherapy and

                    -  Received at least one chemotherapy regimen containing anthracycline;

                    -  Definition of line: Stable disease (SD) after receiving a first-line therapy
                       for at least 4 cycles or progressive disease (PD), and SD after a
                       second-line therapy for at least 2 cycles or PD .

             a.c. In relapsed or refractory status at screening:

               -  Definition of relapse: Remission (including partial remission (PR) or complete
                  remission (CR)) after treatment with at least the standard therapy regimen (it
                  must contain Ribuximab), and then PD;

               -  Definition of refractoriness:

             Non-responsiveness to the last therapy: The best response by the last therapy is SD or
             PD; Relapse or progression after ASCT, including: Relapse (it must be proved by
             biopsy) or PD within 12 months after ASCT; if a rescue therapy is received, the
             patient is non-responsive (SD or PD) to the last therapy;

             • For transformed follicular lymphoma (TFL), patients must be treated adequately
             against FL, and after transformation, must have received at least once the therapy
             against TFL, and become relapsed or refractory after the last therapy.

          4. Measurable imaging lesion at screening: Intranodal lesion must have a long diameter of
             more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm
             (per revised IWG Response Criteria 2014 in Lymphomas);

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;

          6. Adequate bone marrow reserve, defined as:

               -  Absolute neutrophil count (ANC) > 1.0×109/L;

               -  Absolute lymphocyte count (ALC) ≥ 0.3×109/L;

               -  Platelet (PLT) ≥50×109/L;

          7. Proper organ function, complying with the following criteria (except hepatic
             dysfunction due to tumor cell infiltration): Aspartate aminotransferase (AST) ≤ 3
             Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) ≤ 3 ULN; Total serum
             bilirubin ≤ 2 ULN, unless there exists concurrent Gilbert syndrome; patients with
             Gilbert syndrome, with total serum bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN,
             may be included; Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥
             60 mL/min (Cockcroft-Gault formula); Minimum pulmonary reserve, defined as Grade ≤ 1
             dyspnea, and blood oxygen saturation > 91% at non-oxygen inhalation status;
             International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin
             time (aPTT) ≤ 1.5 ULN.

          8. Vascular conditions for apheresis;

          9. Women with child-bearing potential are negative in blood/urine pregnancy tests within
             3 d prior to apheresis, and prior to infusion of CNCT19 cell injection infusion; any
             male or female patient with child-bearing potential must agree to adopt effective
             contraceptive measures throughout the study, and at least half a year after
             administration of the investigational therapy. As judged by the investigator, a
             patient with child-bearing potential means that: He/she has normal sexual life and is
             biologically fertile to have children. Non-fertile female patients (i.e., complying
             one of the following criteria):Previously received hysterectomy, bilateral
             ovariectomy, or bilateral tubal ligation, or Medically confirmed ovarian failure, or
             Medically confirmed postmenopause (amenorrhea of at least 12 consecutive months).

        Exclusion Criteria:

          1. Patients with active central nervous system (CNS) lymphoma (a patient with CNS disease
             symptoms must receive lumbar puncture and MRI/CT to exclude CNS lymphoma).

          2. Patients with existing central nervous system disease or with a history of central
             nervous system disease, e.g., epileptic seizure, cerebral ischemia/hemorrhage,
             paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease,
             cerebellum disease, organic brain syndrome, mental disease, or any autoimmune disease
             involved with central nervous system.

          3. Patients receiving any of the following drugs or therapies within the specified period
             prior to apheresis:

               -  Alemtuzumab within 6 months prior to apheresis;

               -  Cladribine within 3 months prior to apheresis;

               -  Anti-CD20 monoclonal antibody within 7 d prior to apheresis;

               -  Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis;

               -  Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis;

               -  Lenalidomide within 1 d prior to apheresis;

               -  Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than
                  3 half-lives prior to apheresis is eligible;

               -  Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than
                  3 half-lives prior to apheresis is eligible;

               -  Radiotherapy within 6 weeks prior to apheresis, including big bone marrow area
                  (e.g., sternum or pelvis) - progressive disease at radiotherapy site, or PET
                  positive lesion at other non-radiotherapy site is eligible; if there is existing
                  PET positive lesion in other non-radiotherapy sites, then it is allowable to
                  conduct radiotherapy at a single lesion within 2 weeks prior to apheresis.

          4. Patients receiving chemotherapy within 2 weeks prior to CNCT19 Cell injection
             infusion, excluding the following conditions:

               -  Pretreatment chemotherapy as specified by the protocol;

               -  CNS lymphoma prophylaxis by intrathecal injection (it must be stopped within 1
                  week prior to infusion of CNCT19 Cell Injection).

          5. Discontinuation of a systematic therapeutic hormone within 72 h prior to infusion of
             CNCT19 Cell Injection; however, use of the hormone in the physiological surrogate
             amount is eligible (e.g., Prednisone in a dose of <10 mg/d or equivalent).

          6. Patients previously received CAR-T cell therapy.

          7. Patients who have previously received allogeneic hematopoietic stem cell
             transplantation (allo-HSCT).

          8. Patients with known systemic vasculitis (e.g., Wegener granuloma and polyarteritis),
             systemic lupus erythematosus, concurrent active or uncontrolled autoimmune disease
             (e.g., Crohns disease, rheumatoid arthritis, or autoimmune hemolytic anemia), primary
             or secondary immunodeficiency (e.g., HIV infection or severe infectious disease).

          9. Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B
             e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core
             antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of
             detection, hepatitis C antibody (HCV-Ab) positive, anti-treponemia pallidum antibody
             (TP-Ab) positive, EBV-DNA, and CMV-DNA copies being more than the lower limit of
             detection.

         10. Patients who received a major surgery within 4 weeks prior to screening, and are not
             eligible for enrollment as judged by the investigator.

         11. Patients with concurrent active malignancy; those with a history of malignancy, cured
             for≥2 years, are eligible.

         12. Patients complying any of the following conditions: Left ventricular ejection fraction
             (LVEF) ≤45% (ECHO); New York Heart Association (NYHA) Grade III or IV congestive heart
             failure; Severe arrhythmia requiring treatment, including QTc interval≥450 ms in
             males, or ≥470 ms in females (QTcB = QT/RR1/2); Uncontrolled hypertension (systolic
             blood pressures≥140mmHg and/or diastolic blood pressures ≥90 mmHg), pulmonary
             hypertension, or unstable angina pectoris; Myocardial infarction or bridging or stent
             procedure within 12 months prior to administration of the drug; Clinically significant
             valvular heart disease; Other heart diseases unsuitable for enrollment, as judged by
             the investigator.

         13. Patients with lymphoma involved with atrium or ventricle.

         14. Patients with clinical emergency (e.g., intestinal infarction or vascular compression)
             requiring treatment, due to existing lymphoma body obstruction or compression at
             screening.

         15. Patients with active hemorrhage at screening.

         16. Patients with deep vein thrombosis within 6 months prior to screening, or a history of
             pulmonary embolism.

         17. Patients who are known with a history of hypersensitivity reaction to any ingredient
             used for the drug product in the trial.

         18. Patients vaccinated with a live vaccine within 6 weeks prior to screening.

         19. Patients with active infection at screening.

         20. Patients with a life expectancy of less than 3 months.

         21. Patients participating in any other interventional clinical study or receiving
             treatment of an active investigational drug within 3 months prior to CNCT19 Cell
             Injection infusion, or who are planned to participate in another clinical study or to
             receive an antitumor therapy not specified in the protocol.

         22. Patients with other conditions that are not suitable to participate in the clinical
             trial, as considered by the investigator.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
Time Frame:3 months
Safety Issue:
Description:Efficacy of CNCT19 as measured by ORR during the 3 months after CNCT19 Cell Injection infusion, which includes CR and PR.

Secondary Outcome Measures

Measure:Complete Remission (CR)
Time Frame:3 months
Safety Issue:
Description:Efficacy of CNCT19 as measured by CR during the 3 months after CNCT19 Cell Injection infusion.
Measure:ORR(CR+PR)/CR
Time Frame:28 days
Safety Issue:
Description:
Measure:ORR(CR+PR)/CR
Time Frame:6 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:PFS means duration from the CNCT19 Cell Injection infusion to progression of lymphoma, or death for any reason.
Measure:Disease-free survival (DFS)
Time Frame:24 months
Safety Issue:
Description:DFS means duration from the beginning of complete remission to relapse of disease, or death (for any reason).
Measure:Duration of Remission (DOR)
Time Frame:24 months
Safety Issue:
Description:DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.
Measure:Best Overall Response (BOR)
Time Frame:24 months
Safety Issue:
Description:The best overall response after CNCT19 infusion.
Measure:Overall Survival (OS)
Time Frame:24months
Safety Issue:
Description:OS means duration from the CNCT19 Cell Injection infusion to death for any reason, or the last follow-up for survival.
Measure:Time to remission (TTR)
Time Frame:24 months
Safety Issue:
Description:TTR means duration from the CNCT19 Cell Injection infusion to the first response (irrespective of PR or CR, which comes first).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Juventas Cell Therapy Ltd.

Last Updated

October 8, 2020