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A Clinical Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Injection (CNCT19) in the Treatment of Cluster of Differentiation 19 (CD19) Positive Relapsed or Refractory B Cell Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04011293
Recruitment Status : Recruiting
First Posted : July 8, 2019
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Juventas Cell Therapy Ltd.
Information provided by (Responsible Party):
Chunyan Ji, Shandong University

Brief Summary:
This is a single arm, open-label, single center study to determine the safety and efficacy of CNCT19 in adult patients with Relapsed or Refractory B cell Malignancies.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Hematological Malignancies Biological: CNCT19 Early Phase 1

Detailed Description:
This is a single arm, open-label, single-center study to determine the safety and efficacy of CNCT19 in adult patients with r/r B cell Malignancies. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Study of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory B Cell Malignancies
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : April 2022

Arm Intervention/treatment
Experimental: A
Single dose of CNCT19
Biological: CNCT19
0.5 to 4 x 10^6 autologous CNCT19 transduced cells per kg body weight, with a maximum dose of 4 x 10^8 autologous CNCT19 transduced cells via intravenous infusion.




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 24 months ]
  2. Overall remission rate (ORR) [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Response at Day 28±3 days [ Time Frame: 1 month ]
  2. Percentage of patients who achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) (partial remission,PR) at month 6 without SCT between CNCT19 infusion and Month 6 response assessment. [ Time Frame: 6 months ]
  3. Percentage of patients who achieve CR or CRi (PR) with minimal residual disease negative bone marrow. [ Time Frame: 6 months ]
  4. Relapse-free survival [ Time Frame: 24 months ]
  5. Progression-free survival [ Time Frame: 24 months ]
  6. Percentage of patients who achieve best overall response (BOR) [ Time Frame: 24 months ]
  7. Duration of remission (DOR) [ Time Frame: 24 months ]
  8. Overall survival [ Time Frame: 24 months ]
  9. Percentage of patient who achieve CR or CRi (PR) and then proceed to stem cell transplantation(SCT) while in remission. [ Time Frame: 24 months ]
  10. Proportion of patients with detectable replication competent lentivirus (RCL) by vesicular stomatitis virus, glycoprotein (VSV-G) [ Time Frame: at Month 3 post treatment then Month 6 and Month12, yearly until year 15 if CD19 chimeric antigen receptor (CAR) transgene is still detected ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent is signed by a subject or his lineal relation.
  2. Age 18 or older.
  3. Relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL)

    • Relapsed or refractory

      • Relapse within 12 months of first remission
      • Without remission after 2 cycles of induction chemotherapy regimen.
      • Without remission after more than 6 weeks of induction chemotherapy.
      • 2nd or greater Bone Marrow (BM) relapse
      • Any BM relapse after autologous/allogeneic stem cell transplantation (SCT)
    • documentation of cluster of differentiation 19 (CD19) tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry.
    • Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 1generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a BCR-ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) mutation.
    • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment or minimal residual disease (MRD) positive at screening
  4. Relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with CD19-positive after two systemic lines of therapy

    • 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 most recent therapy with duration no longer than 6 month from last dose of therapy
      • Refractory post-autologous stem cell transplant (ASCT) or allogeneic stem cell transplantation (allo-HSCT).

        i. Disease progression or relapsed less than or equal to 12 months of ASCT /allo-HSCT (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/allogeneic stem cell transplantation (SCT).

    • Individuals must have received two systemic lines of therapy

      • anti-cluster of differentiation 20 (CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative and
      • an anthracycline containing chemotherapy regimen
  5. Relapsed or refractory chronic lymphocytic leukemia (CLL) with CD19-positive Diagnosis of CLL that meets 2008 the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria, must have at least one of the following criteria.

    • Patients with Del(17p) / tumour suppressor p53 (TP53) mutation
    • CLL relapsed or refractory after 2 or more lines of therapy, Relapsed is defined as evidence of disease progression after a period of 6 months or more following an initial CR or PR.

    Refractory disease is defined as failure to achieve a response after 6 cycles of induction chemotherapy or having disease progression within 6 months of the last treatment.

  6. At least one measurable lesion, defined as at least 1 lymph node >1.5 cm in the longest diameter, per revised IWG Response Criteria.
  7. Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
  8. Adequate organ function defined as:

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3 upper limit of normal (ULN)
    • 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.
    • A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min(Cockcroft and Gault)
    • Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation > 91% on room air.
    • International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN.
  9. Women of child-bearing potential and all male participants must use highly effective methods of contraception for a period of 1 year after the CNCT19 infusion.

Exclusion Criteria:

  1. Active central nervous system (CNS) involvement by malignancy.
  2. 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.)
  3. Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
  4. During the first four weeks of screening, the patient underwent major surgery which was assessed by the investigator as unsuitable for enrollment;
  5. The patient's heart fits any of the following conditions:

    Left Ventricular Ejection Fraction (LVEF) ≤45%; III/IV congestive heart failure (NYHA); Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular tachycardia); corrected QT interval (QTc)≥450ms (male)or QTc≥470ms (female)(QTc using Bazett's(QTcB)=QT/RR^0.5); Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery.

    Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.

  6. Patients with a history of epilepsy or other active central nervous system diseases.
  7. Has had treat with live vaccine within 6 weeks prior to screening;
  8. Patients with evidence of currently uncontrollable serious active infections (e.g., sepsis, bacteremia, fungemia, viremia, etc.).
  9. Life expectancy < 12 weeks.
  10. Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04011293


Contacts
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Contact: Chuanli Zhao, Dr. ‭+86 185 6008 7009‬ chuanlizhao@163.com

Locations
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China, Shandong
Qilu Hospital of Shandong University Recruiting
Jinan, Shandong, China, 250012
Contact: Chuanli Zhao, Dr.    ‭+86 185 6008 7009‬    chuanlizhao@163.com   
Principal Investigator: Chunyan Ji, Dr.         
Sponsors and Collaborators
Shandong University
Juventas Cell Therapy Ltd.
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Responsible Party: Chunyan Ji, Professor, Shandong University
ClinicalTrials.gov Identifier: NCT04011293    
Other Study ID Numbers: HY001003
First Posted: July 8, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chunyan Ji, Shandong University:
Relapsed
Refractory
Malignancy
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases