Clinical Trials /

A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

NCT04230473

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 acute lymphoblastic leukemia.

Related Conditions:
  • Acute Lymphoblastic Leukemia
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 Acute Lymphoblastic Leukemia
  • Official Title: A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: HY-CD19 CART-001
  • NCT ID: NCT04230473

Conditions

  • Relapsed or Refractory Acute Lymphoblastic Leukemia

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 acute lymphoblastic leukemia.

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 acute
      lymphoblastic leukemia. 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 ALL

               1. Relapse within 12 months of first remission;

               2. Without remission after more than 6 weeks of induction chemotherapy or without
                  remission after 2 cycles of induction chemotherapy regimen;

               3. 2nd or greater Bone Marrow (BM) relapse OR;

               4. First relapse after chemotherapy, without remission after at least 1 rescue
                  treatment;

               5. Any BM relapse after autologous stem cell transplantation (SCT).

          4. Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood
             within 3 months of study entry.

          5. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
             intolerant to or have failed 1 generation and/or 2 generation of tyrosine kinase
             inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I
             mutation.

          6. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.

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

          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. Isolated extra-medullary disease relapse.

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

               1. Lymphodepleting Chemotherapy prescribed by the protocol;

               2. Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped > 72 hours prior
                  to CNCT19 infusion;

               3. The following drugs must be stopped > 1 week prior to CNCT19 infusion:
                  6-mercaptopurine, 6-thioguanine, methotrexate (<25 mg / m2), cytosine arabinoside
                  (<100 mg / m2 / d), vincristine, asparaginase;

               4. Pegylated-asparaginase must be stopped > 4 weeks prior to CNCT19 infusion;

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

          4. Radiotherapy before CNCT19 infusion:

             Non-CNS site of radiation completed < 2 weeks prior to CNCT19 infusion; CNS directed
             radiation completed < 8 weeks prior to CNCT19 infusion.

          5. Therapeutic systemic doses of steroids were stopped < 72 hours prior to CNCT19
             infusion. However, the following physiological replacement doses of steroids are
             allowed: < 10 mg/day hydrocortisone or equivalent.

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

          7. 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.).

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

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

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

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

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

         17. Life expectancy < 12 weeks.

         18. Patient in other interventional clinical studies within 3 months before screening, 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.

         19. 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 Complete Remission with Incomplete Blood Count Recovery (CRi)
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 CRi.
Measure:Overall Remission Rate (ORR)
Time Frame:28 days
Safety Issue:
Description:Description: ORR includes CR and CRi.
Measure:Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow
Time Frame:28 days
Safety Issue:
Description:MRD negative status as determined by central laboratory using multi-parameter flow cytometry.
Measure:Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow
Time Frame:3 months
Safety Issue:
Description:MRD negative status as determined by central laboratory using multi-parameter flow cytometry.
Measure:Overall Remission Rate (ORR)
Time Frame:6 months
Safety Issue:
Description:ORR includes CR and CRi.
Measure:Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow
Time Frame:6 months
Safety Issue:
Description:MRD negative status as determined by central laboratory using multi-parameter flow cytometry.
Measure:Duration of remission (DOR)
Time Frame:24 months
Safety Issue:
Description:DOR is defined as the time from the first documented CR or Partial Remission (PR) to the date of the first documented progressive disease(PD) or death due to any cause.
Measure:Relapse-free survival (RFS)
Time Frame:24 Months
Safety Issue:
Description:RFS is defined as the time from the documented CR or PR after the CNCT19 infusion to the date of the documented PD or death due to any cause.
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 14, 2020