CD7 CAR-T Bridging to alloHSCT for R/R CD7+Malignant Hematologic Diseases

Study Overview
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Brief Summary
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This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with CD7-positive relapsed or refractory Malignant Hematologic Diseases

Official Title
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A Study to Evaluate the Efficacy and Safety of CD7CAR-T Bridging to Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed CD7 Positive Malignant Hematologic Diseases

Conditions
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Hematologic Diseases, Neoplasms

Intervention / Treatment
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* Drug: CD7 CAR-T cells injection
* Other: Allogeneic hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form (ICF) Male or female, 18-75 years old Anticipated survival time more than 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status ≤2 According to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphocytic Leukemia and Acute Myeloid Leukemia (2016. v1), patients diagnosed as CD7+ALL and AML Consistent with r/r CD7+acute leukemia diagnosis, including any of the following conditions a. No CR after standard chemotherapy b. The first induction reaches CR, but CR ≤ 12 months c. Patients with r/r CD7+acute leukemia have not responded to the first or multiple remedial treatments d. Multiple recurrences Philadelphia chromosome negative (Ph -) subjects; Or cannot tolerate tyrosine kinase inhibitor (TKI) treatment; Or Philadelphia chromosome positive (Ph+) subjects who did not respond to both TKI treatments Normal lung function, oxygen saturation greater than 92% without oxygen inhalation The blood biochemical test results are consistent with the following results a. (AST) and (ALT) ≤ 2.5 × (ULN) b. Total bilirubin ≤ 1.5 × ULN c. 24-hour serum creatinine clearance ≥ 30 mL/min d. Lipase and amylase ≤ 2 × ULN Fertility capable men and women of childbearing age must agree to use effective contraception starting with the signing of an informed consent form until within 2 years after the use of the study drug. Women of reproductive age include pre menopausal women and women within 2 years after menopause. The blood pregnancy test for women of reproductive age must be negative at screening Exclusion Criteria: Patients with the history of epilepsy or other CNS disease Pregnant or breastfeeding Active infection with no cure Patients with prolonged QT interval time or severe heart disease Have experienced hypersensitivity or intolerance to any drug used in this study Patients who received anticancer chemotherapy or other drug treatment within 2 weeks before screening Previous malignant tumors that require treatment or have evidence of recurrence within the previous 5 years of screening Clinically significant central nervous system lesions such as seizures, cerebral vascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement, or cancerous meningitis In the past 2 years, terminal organ damage caused by autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) or the need for systematic application of immunosuppressive or other systemic disease control drugs Severe active viral, bacterial, or uncontrolled systemic fungal infections; Genetic bleeding/coagulation disorders, a history of non-traumatic bleeding or thromboembolism, and other diseases that may increase the risk of bleeding Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during this study Participated in clinical trials of other drugs within 4 weeks or 5 drug half-lives (T1/2) before screening Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>R/R CD7+Malignant Hematologic Diseases | Drug: CD7 CAR-T cells injection<br>* CD7 CAR T cells treat patients with refractory or relapsed CD7 positive Malignant Hematologic Diseases<br>Other: Allogeneic hematopoietic stem cell transplantation<br>* In this study, Allogeneic hematopoietic stem cell transplantation is used as a bridge therapy to CD7 CAR T cells infusion to treat patients with refractory or relapsed CD7 positive Malignant Hematologic Diseases<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and level of AE and SAE | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD7 CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAR-T cell expression | CAR-T cell expression in vivo | Evaluate at 1, 2, 3, 4, 8,12,16, 20 and 24 weeks after CAR-T infusion | 
| CAR-T related cytokine expression | CAR-T related cytokine expression | Evaluate at 1, 2, 3 and 4 weeks after CAR-T infusion | 
| Survival Rate （SR） | Survival Rate （SR） | Evaluate at 6, 9, and 12 months | 
| Time-To-Progression（TTP） | Time from the beginning of treatment to the progression of the disease | Month 2,3,4,6,12,18and 24 | 
| Progression-free survival (PFS) | Assessment of PFS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| Duration of remission,DOR | The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion | Up to 1 years after Treatment | 
| Overall response rate,ORR | The proportion of patients with CR (complete remission) /CRi (complete remission with incomplete blood count recovery); The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response). | Evaluate at 4, 8, and 12 weeks after CAR-T infusion | 
| Clinical Benefit Rate（CBR） | ORR+MR | Up to 24 weeks after Treatment | 
| Disease Control Rate （DCR） | CBR+SD | Up to 12 weeks after Treatment | 
| Overall survival, OS | The time from CAR-T infusion to death due to any cause | Up to 1 years after Treatment | 
| Minimal Residual Disease | MRD in CR and sCR patients | Up to 2 years after Treatment | 
| Bone marrow transplantation STR | Monitoring the status of allogeneic hematopoietic stem cell transplantation using STR-PCR | Evaluate at 4, 8,12,16 and 20 weeks after allogeneic hematopoietic stem cell transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allo-HSCT, CD7 CAR-T