Cell Therapy for CD7 Positive Acute Myeloid Leukemia or Mixed Lineage Leukemia

Leukemia, T Cell Clinical Trial

Official title:

Cell Therapy for CD7 Positive Acute Leukemia or Mixed Lineage Leukemia Except Those Who Are Diagnosed With T-ALL/T-LBL Using CD7-Specific CAR-T Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04938115
• Other study ID #: CD7+ mixed lineage leukemia
• Status: Completed
• Phase: N/A
• Start date: May 10, 2021
• Est. completion date: October 30, 2023

Study information

• Verified date: May 2023
• Source: Hebei Senlang Biotechnology Inc., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL

Description:

The CARs consist of an anti-CD7 VHHs, 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 CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL

The Secondary research objectives:

To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 30, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of refractory or relapsed CD7+ acute myeloid leukemia or mixed lineage leukemia was made according to the NCCN 2019.V2 guideline. Refractory AML is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed AML is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patient diagnosed with AML should be treated and whose disease failed with at least 2 prior lines of therapies. 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+ expression on tumor cells (CD7 positive blasts =50% by flow cytometry);

3. Life expectancy greater than 12 weeks;

4. KPS or Lansky score=60;

5. HGB=70g/L (can be transfused);

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. Merging 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 on 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 symptomatic disorders of the central nervous system, which include but not limited to uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, and cerebellar disease, etc.;

12. Have received transplant treatment for less than 6 months in prior to enrollment;

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, T Cell
• Leukemia, T-Cell

Intervention

Biological:
• CD7 CART
Biological: CD7 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis

Locations

Country	Name	City	State
China	He bei Yan da Lu dao pei Hospital	Beijing	Hebei

Sponsors (1)

Lead Sponsor	Collaborator
Hebei Senlang Biotechnology Inc., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence and severity of adverse events	To evaluate the possible adverse events occurred within first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity	First 1 month post CAR-T cells infusion
Primary	Efficacy: Remission Rate	In the presence of extramedullary lesions, complete remission (CR), partial remission (PR), stable disease (SD), disease recurrence or progression (PD) shall be used to describe extramedullary lesions	3 months post CAR-T cells infusion
Secondary	duration of response (DOR)	duration of response (DOR)	24 months post CAR-T cells infusion
Secondary	Efficacy: progression-free survival (PFS)	progression-free survival (PFS) time	24 months post CAR-T cells infusion
Secondary	CAR-T proliferation	the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method	3 months post CAR-T cells infusion
Secondary	CAR-T proliferation	percentage of CD7 CAR- T cells measured by flow cytometry method	3 months post CAR-T cells infusion
Secondary	Cytokine release	Cytokine( IL-6,IL-10,IFN-?,TNF-a ) concentration (pg/mL) by flow cytometry method	First 1 month post CAR-T cells infusion
Secondary	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	24 months post CAR-T cells infusion
Secondary	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	First 1 month post CAR-T cells infusion