Clinical Trials /

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

NCT04232826

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Transformed Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Diffuse Non-Hodgkin Lymphoma
  • Official Title: A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Diffuse Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: HY-CD19 CART-002
  • NCT ID: NCT04232826

Conditions

  • Diffuse Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
single dose of CNCT19Single dose of CNCT19

Purpose

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.

Detailed Description

      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. The study will have the following sequential phases: Screening,
      Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and
      Follow-up, and Survival Follow-up. The total duration of the study is 2 years from CNCT19
      cell infusion.
    

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. Informed consent is signed by the subject.

          2. Age 18 to 75.

          3. 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.

          4. At least one measurable lesion, defined as at least 1 lymph node >1.5 cm in the
             longest diameter, per revised IWG Response Criteria.

          5. 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).

          6. Eastern cooperative oncology group (ECOG) performance status of 0 to 1.

          7. Sufficient bone marrow reserves defined as:

               1. Absolute neutrophil (ANC) > 1,000 / mm3;

               2. Lymphocyte absolute value (ALC) ≥ 100 / mm3;

               3. Platelet (PLT) ≥ 50,000 / mm3.

          8. Adequate organ function defined as:

               1. aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN);

               2. Serum alanine aminotransferase (ALT) ≤ 3 upper limit of normal (ULN);

               3. Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome; Note:
                  Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤
                  1.5 ULN will be eligible;

               4. A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min (Cockcroft and
                  Gault);

               5. Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen
                  saturation > 91% on room air;

               6. International normalized ratio (INR) ≤ 1.5 ULN and activated partial
                  thromboplastin time (APTT) ≤ 1.5 ULN;

          9. Non-hematological toxic reactions (excluding diseases related) caused by previous
             treatment were restored to ≤ 1 level before screening (excluding ≤ 2 level of
             neurotoxicity caused by hair loss and chemotherapy drugs).

         10. Women of childbearing age have a negative blood / urine pregnancy test within 7 days
             before the CNCT19 infusion. Women of child-bearing potential and all male participants
             must use highly effective methods of contraception throughout the study and for a
             period of at least six months after the CNCT19 infusion.

        Exclusion Criteria:

          1. Active CNS involvement by malignancy.

          2. Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The
             following situations are excluded:

               1. Lymphodepleting Chemotherapy prescribed by the protocol;

               2. CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion.

          3. Has had treatment with any prior anti-CD19 therapy.

          4. Plans to receive autologous stem cell transplantation (ASCT) within 6 weeks before the
             CNCT19 infusion.

          5. Patients who have previously received Allogeneic Hematopoietic Stem Cell
             Transplantation (allo-HSCT).

          6. 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.).

          7. Patients who are positive for any of HBsAg, HCV-Ab, TP-Ab.

          8. Patients who have previously received surgery within 4 weeks before the screening that
             was unsuitable for enrollment by the investigator's assessment.

          9. 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.

         10. 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.

         11. Clinically significant pleural effusion.

         12. Patients with a history of epilepsy, cerebrovascular ischemia / hemorrhage, cerebellar
             disease or other active central nervous system diseases.

         13. Lymphoma affects the atrium or ventricle.

         14. Clinical emergencies (such as intestinal obstruction or vascular compression) that
             requires urgent treatment due to obstruction or compression of lymphoma tumors during
             screening.

         15. History of deep vein thrombosis or pulmonary embolism within 6 months of screening.

         16. Known history of hypersensitivity to ingredients used in the drug.

         17. Has had treat with live vaccine within 6 weeks prior to screening.

         18. Patients with evidence of currently uncontrollable serious active infections (e.g.,
             sepsis, bacteremia, fungemia, viremia, etc.).

         19. Life expectancy < 12 weeks.

         20. Patient in other interventional clinical studies within 3 months before the CNCT19
             infusion, who have received active drug therapy, or who intend to participate in
             another clinical trial or receive anti-tumor therapy outside the protocol during the
             entire study.

         21. Patients with other conditions making the patients unsuitable for receiving cell
             therapy as judged by the investigator.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)
Time Frame:28 days
Safety Issue:
Description:Determine the MTD and DLT of CNCT19 in the Treatment and recommend the dose for Phase II study.

Secondary 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 infusion, which includes CR and PR.
Measure:Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
Time Frame:28 days
Safety Issue:
Description:Efficacy of CNCT19 as measured by ORR during the 28 days after CNCT19 infusion, which includes CR and PR.
Measure:Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
Time Frame:2 months
Safety Issue:
Description:Efficacy of CNCT19 as measured by ORR during the 2 months after CNCT19 infusion, which includes CR and PR.
Measure:Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
Time Frame:6 months
Safety Issue:
Description:Efficacy of CNCT19 as measured by ORR during the 6 months after CNCT19 infusion, which includes CR and PR.
Measure:Best Overall Response (BOR)
Time Frame:24 months
Safety Issue:
Description:The best overall response after CNCT19 infusion.
Measure:Time to initial Response (TTR)
Time Frame:6 months
Safety Issue:
Description:TTR is defined as the time from the CNCT19 infusion to the first documented CR or PR.
Measure:Progression-free survival (RFS)
Time Frame:24 months
Safety Issue:
Description:PFS is defined as the time from the signing of informed consent form to the date of the documented progressive disease(PD) or death due to any cause.
Measure:Duration of remission (DOR)
Time Frame:24 months
Safety Issue:
Description:DOR is defined as the time from the first documented CR or PR to the date of the first documented relapse or PD.
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:OS is defined as the time from the signing of informed consent form to the date of the last survival follow-up or death due to any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Juventas Cell Therapy Ltd.

Last Updated

January 16, 2020