CD7 CAR-T Cell Treatment of Relapsed/Refractory CD7+ T -Acute Lymphoblastic Leukemia/ Lymphoma

Phase 1

• Conditions: Relapsed/Refractory, High Risk Hematologic Malignancies; T-ALL/Lymphoma
• Interventions: Biological: CD7CAR T cells

• Registration Number: NCT05212584
• Lead Sponsor: iCell Gene Therapeutics

Brief Summary

This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD7 CAR-T cells in patients with relapsed and/or refractory, high risk hematologic malignancies.

Detailed Description

T-acute lymphoblast leukemia (T-ALL) accounts for 15-20% of all ALL cases. It is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. T-ALL is a highly aggressive tumor. Adults need intensive chemotherapy, and the cure rate is \<50%, even with stem cell transplantation. The prognosis is also very poor. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there is limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. Since 95% of T-ALLs express CD7, this might provide an effective targeting approach for the vast majority of T-ALL cases.

Study Timeline

• Status Verified: 2022-01
• Study First Submitted: 2022-01-16
• Study First Submitted QC: 2022-01-16
• Study First Posted: 2022-01-28
• Last Update Submitted: 2022-06-30
• Study Start: 2022-07-01
• Last Update Posted: 2022-07-06
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• 1. Signed written informed consent; Patients volunteer to participate in the clinical trial; 2. Diagnosis is mainly based on the World Health Organization (WHO) 2008; 3. Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%; 4. Leukemic blast cells express CD7 (CD7 positive by flow cytometry or immunohistochemistry ≥70%); 5. The expected survival period is greater than 12 weeks; 6. ECOG score ≤2; 7. Age 2-60 years old; 8. HGB≥70g/L (can be transfused); 9. Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.

Exclusion Criteria

• 1. Patients declining to consent for treatment 2. Prior solid organ transplantation 3. One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV; 4. History of severe pulmonary dysfunction diseases; 5. Severe infection or persistent infection cannot be effectively controlled; 6. Severe autoimmune disease or congenital immunodeficiency; 7. Active hepatitis; 8. Human immunodeficiency virus (HIV) infection; 9. Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CD7 CAR T cells	CD7CAR T cells	Dose escalation phase: CD7 CAR T cells will be transduced with a lentiviral vector to express a CD7 CARs. with an escalation approach, 1 e6 to 7 e6 CAR-T cells/kg

Primary Outcome Measures

Name	Time	Method
The number and incidence of adverse events after CD7 CAR infusion.	Up to 3 months	Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR infusion

Secondary Outcome Measures

Name	Time	Method
Evaluation of curative effects	Up to 1 year	Evaluation of curative effects within 1 year including 1)completion remission (CR), 2) complete remission with incomplete recovery of blood cells (CRi), 3) minimal residual disease positive (MRD+), 4)minimal residual disease negative (MRD-), and 4) disease recurrence or progression
Disease response to CD7 CAR T cells	Up to 1 year	The disease response to CD7 CAR T cells is evaluated by bone marrow biopsy and aspirate within 1 years after CAR infusion. The proportion of subjects receiving CD7 CAR T infusion to 1) morphological remission (blasts \<5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable).
Overall survival	Up to 1 year	Overall survival {1 year after CAR infusion\] . The time from the start of CD7 CAR T injection to death is determined as the overall survival

Trial Locations

Locations (1)

Hebei Yanda Lu Daopei Hospital; 🇨🇳 Langfang, Hebei, China