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

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

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

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Hematologic Diseases
• Intervention / Treatment: Drug: CD7 CAR-T cells injection; Other: Allogeneic hematopoietic stem cell transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: He Huang, MD; Phone Number: +86-0571-87236476; Email: hehuangyu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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
Progression-free survival (PFS)	Assessment of PFS at Month 6,12,18and 24	Month 6,12,18and 24
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
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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2023
• Primary Completion (Anticipated): April 25, 2025
• Study Completion (Anticipated): April 25, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: allo-HSCT; CD7 CAR-T
• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: TXB2022023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No