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Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells

Primary Purpose

T-cell Acute Lymphoblastic Leukemia/Lymphoma

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD7 CAR-T
Sponsored by
Hebei Senlang Biotechnology Inc., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-cell Acute Lymphoblastic Leukemia/Lymphoma focused on measuring T-ALL,T-LBL , CD7,CAR-T

Eligibility Criteria

2 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden >5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible.
  2. CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden >5%,or MRD+, or new extramedullary lesions reappeared.
  3. Life expectancy greater than 12 weeks
  4. KPS or Lansky score≥60
  5. HGB≥70g/L
  6. oxygen saturation of blood>90%
  7. Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal
  8. Informed consent explained to, understood by and signed by patient/guardian.

Exclusion Criteria:

  1. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment)
  2. Has an active GvHD;
  3. Has a history of severe pulmonary function damaging;
  4. With other tumors which is/are in advanced malignant and has/have systemic metastasis;
  5. Severe or persistent infection that cannot be effectively controlled;
  6. Presence of severe autoimmune diseases or immunodeficiency disease;
  7. Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
  8. Patients with HIV infection or syphilis infection;
  9. Has a history of serious allergies to biological products (including antibiotics);
  10. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
  11. Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
  12. Received allogeneic hematopoietic stem cell transplantation within 6 months;
  13. Being pregnant and lactating or having pregnancy within 12 months;
  14. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Sites / Locations

  • Hebei yanda Ludaopei Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD7 CAR-T

Arm Description

Patients will be treated with CD7 CAR-T cells

Outcomes

Primary Outcome Measures

Safety: Incidence and severity of adverse events
To evaluate the possible adverse events occurred within the first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
Efficacy: Remission Rate
Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、partial remission(PR), No remission(NR), overall remission (OR)

Secondary Outcome Measures

duration of response (DOR)
duration of response (DOR)
Efficacy: progression-free survival (PFS)
progression-free survival (PFS) time
CAR-T proliferation
the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method
CAR-T proliferation
percentage of CD7 CAR- T cells measured by flow cytometry method
Cytokine release
Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method
Pharmacokinetics (PK) indicators:
the peak concentration of Senl-T7 CAR-T cells amplified in the peripheral blood (Cmax, detected by flow cytometry and qPCR); the time taken to reach the peak concentration (Tmax), and the persistent time of the Senl-T7 CAR-T cells in vivo in patients;
Pharmacodynamic (PD) indicators:
the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point

Full Information

First Posted
September 27, 2020
Last Updated
June 23, 2021
Sponsor
Hebei Senlang Biotechnology Inc., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04572308
Brief Title
Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Official Title
Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
May 30, 2021 (Actual)
Study Completion Date
May 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hebei Senlang Biotechnology Inc., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (TLBL).
Detailed Description
The CARs consist of an anti-CD7 single-chain variable fragment(scFv), a portion of the human CD137(4-1BB) molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy. The Main research objectives: To evaluate the safety and efficacy of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL The Secondary research objectives: To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-cell Acute Lymphoblastic Leukemia/Lymphoma
Keywords
T-ALL,T-LBL , CD7,CAR-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CD7 CAR-T
Arm Type
Experimental
Arm Description
Patients will be treated with CD7 CAR-T cells
Intervention Type
Biological
Intervention Name(s)
CD7 CAR-T
Intervention Description
Patients will be treated with CD7 CAR-T cells Biological: CD7 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;
Primary Outcome Measure Information:
Title
Safety: Incidence and severity of adverse events
Description
To evaluate the possible adverse events occurred within the first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
Time Frame
First 1 month post CAR-T cells infusion
Title
Efficacy: Remission Rate
Description
Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、partial remission(PR), No remission(NR), overall remission (OR)
Time Frame
3 months post CAR-T cells infusion
Secondary Outcome Measure Information:
Title
duration of response (DOR)
Description
duration of response (DOR)
Time Frame
24 months post CAR-T cells infusion
Title
Efficacy: progression-free survival (PFS)
Description
progression-free survival (PFS) time
Time Frame
24 months post CAR-T cells infusion
Title
CAR-T proliferation
Description
the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method
Time Frame
3 months post CAR-T cells infusion
Title
CAR-T proliferation
Description
percentage of CD7 CAR- T cells measured by flow cytometry method
Time Frame
3 months post CAR-T cells infusion
Title
Cytokine release
Description
Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method
Time Frame
First 1 month post CAR-T cells infusion
Title
Pharmacokinetics (PK) indicators:
Description
the peak concentration of Senl-T7 CAR-T cells amplified in the peripheral blood (Cmax, detected by flow cytometry and qPCR); the time taken to reach the peak concentration (Tmax), and the persistent time of the Senl-T7 CAR-T cells in vivo in patients;
Time Frame
Long time
Title
Pharmacodynamic (PD) indicators:
Description
the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point
Time Frame
First 1 month post CAR-T cells infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden >5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible. CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden >5%,or MRD+, or new extramedullary lesions reappeared. Life expectancy greater than 12 weeks KPS or Lansky score≥60 HGB≥70g/L oxygen saturation of blood>90% Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal Informed consent explained to, understood by and signed by patient/guardian. Exclusion Criteria: Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment) Has an active GvHD; Has a history of severe pulmonary function damaging; With other tumors which is/are in advanced malignant and has/have systemic metastasis; Severe or persistent infection that cannot be effectively controlled; Presence of severe autoimmune diseases or immunodeficiency disease; Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]); Patients with HIV infection or syphilis infection; Has a history of serious allergies to biological products (including antibiotics); Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6. Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement; Received allogeneic hematopoietic stem cell transplantation within 6 months; Being pregnant and lactating or having pregnancy within 12 months; Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.
Facility Information:
Facility Name
Hebei yanda Ludaopei Hospital
City
Yanda
State/Province
Hebei
Country
China

12. IPD Sharing Statement

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Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells

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