CD7 CAR-T Bridging to alloHSCT for R/R CD7+Malignant Hematologic Diseases
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Group R/R CD7+Malignant Hematologic Diseases |
Drug: CD7 CAR-T cells injection
CD7 CAR T cells treat patients with refractory or relapsed CD7 positive Malignant Hematologic Diseases
Other: Allogeneic hematopoietic stem cell transplantation
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
|
Outcome Measures
Primary Outcome Measures
- Incidence and level of AE and SAE [Baseline up to 28 days after CD7 CAR T-cells infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Secondary Outcome Measures
- CAR-T cell expression [Evaluate at 1, 2, 3, 4, 8,12,16, 20 and 24 weeks after CAR-T infusion]
CAR-T cell expression in vivo
- CAR-T related cytokine expression [Evaluate at 1, 2, 3 and 4 weeks after CAR-T infusion]
CAR-T related cytokine expression
- Survival Rate （SR） [Evaluate at 6, 9, and 12 months]
Survival Rate （SR）
- Time-To-Progression（TTP） [Month 2,3,4,6,12,18and 24]
Time from the beginning of treatment to the progression of the disease
- Progression-free survival (PFS) [Month 6,12,18and 24]
Assessment of PFS at Month 6,12,18and 24
- Duration of remission,DOR [Up to 1 years after Treatment]
The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion
- Overall response rate,ORR [Evaluate at 4, 8, and 12 weeks after CAR-T infusion]
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).
- Clinical Benefit Rate（CBR） [Up to 24 weeks after Treatment]
ORR+MR
- Disease Control Rate （DCR） [Up to 12 weeks after Treatment]
CBR+SD
- Overall survival, OS [Up to 1 years after Treatment]
The time from CAR-T infusion to death due to any cause
- Minimal Residual Disease [Up to 2 years after Treatment]
MRD in CR and sCR patients
- Bone marrow transplantation STR [Evaluate at 4, 8,12,16 and 20 weeks after allogeneic hematopoietic stem cell transplantation]
Monitoring the status of allogeneic hematopoietic stem cell transplantation using STR-PCR
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of signed and dated informed consent form (ICF)
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Male or female, 18-75 years old
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Anticipated survival time more than 12 weeks
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Eastern Cooperative Oncology Group (ECOG) performance status ≤2
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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
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Consistent with r/r CD7+acute leukemia diagnosis, including any of the following conditions
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- No CR after standard chemotherapy
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- The first induction reaches CR, but CR ≤ 12 months
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- Patients with r/r CD7+acute leukemia have not responded to the first or multiple remedial treatments
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- Multiple recurrences
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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
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Normal lung function, oxygen saturation greater than 92% without oxygen inhalation
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The blood biochemical test results are consistent with the following results
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- (AST) and (ALT) ≤ 2.5 × (ULN)
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- Total bilirubin ≤ 1.5 × ULN
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- 24-hour serum creatinine clearance ≥ 30 mL/min
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- Lipase and amylase ≤ 2 × ULN
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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:
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Patients with the history of epilepsy or other CNS disease
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Pregnant or breastfeeding
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Active infection with no cure
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Patients with prolonged QT interval time or severe heart disease
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Have experienced hypersensitivity or intolerance to any drug used in this study
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Patients who received anticancer chemotherapy or other drug treatment within 2 weeks before screening
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Previous malignant tumors that require treatment or have evidence of recurrence within the previous 5 years of screening
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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
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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
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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
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Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during this study
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Participated in clinical trials of other drugs within 4 weeks or 5 drug half-lives (T1/2) before screening
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Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The first affiliated hospital of medical college of zhejiang university | Hangzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- Zhejiang University
- Yake Biotechnology Ltd.
Investigators
- Principal Investigator: He Huang, MD, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TXB2022023