Clinical Trials /

CD7-CART in the Treatment of r / r CD7 Positive Hemolymph System Malignancies on Increasing Dose and Open Label Study

NCT04480788

Description:

Phase I was a single arm, open label, dose increasing study to explore the safety, tolerance and Cytodynamic characteristics of the drug, and to preliminarily observe the efficacy of the study drug in relapsed / refractory CD7 Positive hematolymph system malignant tumor patients, so as to explore the clinical applicable dose of phase II. Since the activity and toxicity of cellular drugs (long-term survival drugs) do not have obvious dose dependence, and the increase of their dose may be accompanied by the increase of toxicity, rather than necessary for therapeutic effect, it is not necessarily suitable to recommend the effective dose according to the maximum tolerable dose (MTD). Therefore, this study will be based on the safety data, as well as the preliminary efficacy, efficacy and drug The end point of pharmacokinetics (ORR, the content of CD7 Positive Cells, the expansion and duration of car-t cells) were comprehensively considered to determine the recommended dose for phase II clinical trial.Main research purposes Objective to evaluate the safety and tolerability of T cell injection targeting CD7 autologous chimeric antigen receptor in the treatment of relapsed / refractory CD7 Positive hematological and lymphoid malignancies.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Anaplastic Large Cell Lymphoma, ALK-Negative
  • Angioimmunoblastic T-Cell Lymphoma
  • Lymphoma
  • Nasal Type Extranodal NK/T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Small Intestinal Lymphoma
  • T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD7-CART in the Treatment of r / r CD7 Positive Hemolymph System Malignancies on Increasing Dose and Open Label Study
  • Official Title: Early Clinical Study on Increasing Dose and Open Label of T Cell Injection Targeting CD7 Autologous Chimeric Antigen Receptor in the Treatment of Relapsed / Refractory CD7 Positive Hemolymph System Malignancies

Clinical Trial IDs

  • ORG STUDY ID: PG-CART-07-001
  • NCT ID: NCT04480788

Conditions

  • T Lymphoblastic Leukemia/Lymphoma
  • Extramedullary NK-T-cell Lymphoma, Nasal Type
  • Peripheral T-cell Lymphoma, Nonspecific
  • Angioimmunoblastic T-cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Anaplastic Large Cell Lymphoma, ALK-negative
  • T-cell Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
T cell injection targeting CD7 chimeric antigen receptorT cell injection targeting CD7 chimeric antigen receptor

Purpose

Phase I was a single arm, open label, dose increasing study to explore the safety, tolerance and Cytodynamic characteristics of the drug, and to preliminarily observe the efficacy of the study drug in relapsed / refractory CD7 Positive hematolymph system malignant tumor patients, so as to explore the clinical applicable dose of phase II. Since the activity and toxicity of cellular drugs (long-term survival drugs) do not have obvious dose dependence, and the increase of their dose may be accompanied by the increase of toxicity, rather than necessary for therapeutic effect, it is not necessarily suitable to recommend the effective dose according to the maximum tolerable dose (MTD). Therefore, this study will be based on the safety data, as well as the preliminary efficacy, efficacy and drug The end point of pharmacokinetics (ORR, the content of CD7 Positive Cells, the expansion and duration of car-t cells) were comprehensively considered to determine the recommended dose for phase II clinical trial.Main research purposes Objective to evaluate the safety and tolerability of T cell injection targeting CD7 autologous chimeric antigen receptor in the treatment of relapsed / refractory CD7 Positive hematological and lymphoid malignancies.

Trial Arms

NameTypeDescriptionInterventions
T cell injection targeting CD7 chimeric antigen receptorExperimental
  • T cell injection targeting CD7 chimeric antigen receptor

Eligibility Criteria

        Inclusion Criteria:

          -  The age ranged from 7 to 70 years (including the cut-off value), regardless of gender

          -  The expected survival time was more than 6 weeks

          -  ECOG score 0-1

          -  Malignant lymphoma (including but not limited to acute T-lymphoblastic leukemia /
             lymphoma; extramedullary NK / T-cell lymphoma, nasal type; peripheral T-cell lymphoma,
             nonspecific; vascular immunoblastic T-cell lymphoma; intestinal disease associated
             T-cell lymphomas; anaplastic large cell lymphoma (ALK -); T-cell lymphoblastic
             leukemia)

          -  When screening, hematological malignancies with CD7 Positive confirmed by bone marrow
             examination or tumor pathology with positive rate of CD7 ≥ 30%, meeting one of the
             following conditions:

               1. At least two chemotherapy regimens failed or did not achieve complete remission
                  or relapse;

               2. Patients who relapsed after stem cell transplantation were not affected by other
                  treatment methods;

          -  For peripheral blood involved acute T-lymphoblastic leukemia / lymphoma and NK /
             T-cell lymphoma, patients with TCR rearrangement were detected by ngs

          -  The liver and kidney function, heart and lung function meet the following
             requirements:

               1. Creatinine ≤ 1.5 ULN;

               2. LVEF ≥ 45%;

               3. Blood oxygen saturation > 91%;

               4. The total bilirubin ≤ 2 × ULN; ALT and AST ≤ 2.5 × ULN; the abnormal ALT and AST
                  caused by diseases (such as liver infiltration or bile duct obstruction) can be
                  relaxed to ≤ 5 × ULN;

          -  Understand the experiment and have signed the informed consent

        Exclusion Criteria:

          -  Those who need immunosuppressant;

          -  For intestinal disease-related T-cell lymphoma, patients with intestinal ulcer or
             hematochezia were examined by colonoscopy;

          -  In addition to cervical carcinoma in situ, basal cell or squamous cell skin cancer,
             local prostate cancer after radical operation, and breast ductal carcinoma in situ
             after radical operation;

          -  The patients with positive HBsAg or HBcAb and HBV DNA titer in peripheral blood were
             not within the normal reference value; those with positive anti HCV antibody and
             positive HCV RNA in peripheral blood; those with HIV antibody positive and
             cytomegalovirus DNA positive Syphilis was positive;

          -  Severe heart disease: including but not limited to unstable angina pectoris,
             myocardial infarction (within 6 months before screening), congestive heart failure
             (NYHA classification ≥ III), severe arrhythmia;

          -  Unstable systemic diseases judged by researchers: including but not limited to severe
             liver, kidney or metabolic diseases requiring drug treatment;

          -  Within 7 days before screening, there were active or uncontrollable infections
             requiring systemic treatment (except for mild genitourinary system infection and upper
             respiratory tract infection);

          -  Pregnant or lactating women, female subjects planning pregnancy within 1 year after
             cell reinfusion or male subjects whose partners plan to conceive within 1 year after
             cell reinfusion;

          -  Patients who had received car-t therapy or other gene modified cell therapy before
             screening;

          -  Subjects who were receiving systemic steroid therapy or were receiving systemic
             steroid therapy for 7 days were excluded;

          -  Participated in other clinical studies within 3 months before screening;

          -  There was evidence of central nervous system invasion during screening;

          -  According to the judgment of the researchers, it does not conform to the condition of
             cell preparation;

          -  Other researchers think it is not suitable to be included in the study.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:7 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT)
Time Frame:Up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety results
Time Frame:Up to 2 years
Safety Issue:
Description:Number of adverse events
Measure:PK
Time Frame:Up to 2 years
Safety Issue:
Description:The maximum concentration (Cmax)
Measure:PK
Time Frame:Up to 2 years
Safety Issue:
Description:the time to reach the maximum concentration (Tmax)
Measure:PK
Time Frame:Up to 2 years
Safety Issue:
Description:The area under the curve (auc0-28d ) at 28d respectively after administration
Measure:PD
Time Frame:Up to 2 years
Safety Issue:
Description:Absolute value of CD7 Positive Cells in peripheral blood at each time point
Measure:PD
Time Frame:Up to 2 years
Safety Issue:
Description:The proportion of CD7 Positive Cells in peripheral blood at each time point
Measure:ORR
Time Frame:Up to 2 years
Safety Issue:
Description:The total response rate was 3 months and 6 months
Measure:overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:Time from initiation of CD7 car-t cell therapy to death (for any reason)
Measure:Search Results Featured snippet from the web Duration of response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:The time from the first assessment of Cr or PR to the first assessment of recurrence or progression of the disease or death from any cause
Measure:Progression-free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:The time from the beginning of treatment with CD7 car-t cells to the first progression of disease or death from any cause
Measure:Immunogenicity
Time Frame:Up to 2 years
Safety Issue:
Description:The positive rate of human anti car antibody at each time point

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Last Updated

July 17, 2020