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

Not Applicable

Completed

• Conditions: Leukemia, T Cell
• Interventions: Biological: CD7 CART

• Registration Number: NCT04938115
• Lead Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

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 CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL

Detailed 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

Study Timeline

• Study Start: 2021-05-10
• Study First Submitted: 2021-06-16
• Study First Submitted QC: 2021-06-16
• Study First Posted: 2021-06-24
• Status Verified: 2023-05
• Primary Completion: 2023-05-31
• Study Completion: 2023-10-30
• Last Update Submitted: 2024-06-13
• Last Update Posted: 2024-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD7 CAR-T	CD7 CART	-

Primary Outcome Measures

Name	Time	Method
Safety: Incidence and severity of adverse events	First 1 month post CAR-T cells infusion	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
Efficacy: Remission Rate	3 months post CAR-T cells infusion	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

Secondary Outcome Measures

Name	Time	Method
Cytokine release	First 1 month post CAR-T cells infusion	Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method
Efficacy: progression-free survival (PFS)	24 months post CAR-T cells infusion	progression-free survival (PFS) time
Pharmacokinetics (PK) indicators	24 months post CAR-T cells infusion	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	First 1 month post CAR-T cells infusion	the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point
duration of response (DOR)	24 months post CAR-T cells infusion	duration of response (DOR)
CAR-T proliferation	3 months post CAR-T cells infusion	percentage of CD7 CAR- T cells measured by flow cytometry method

Trial Locations

Locations (1)

He bei Yan da Lu dao pei Hospital; 🇨🇳 Beijing, Hebei, China