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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory, High Risk Hematologic Malignancies; T-ALL/Lymphoma
• Intervention / Treatment: Biological: CD7CAR T cells

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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Langfang, Hebei, China
      • Recruiting
      • Hebei Yanda Lu Daopei Hospital
      • Contact: Peihua Lu, MD; Phone Number: 011-86-186 1163 6171; Email: peihua_lu@126.com
      • Principal Investigator: Peihua Lu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD7 CAR 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	Biological: CD7CAR T cells; CD7 CAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and incidence of adverse events after CD7 CAR infusion.	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	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease response to CD7 CAR T cells	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).	Up to 1 year
Evaluation of curative effects	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	Up to 1 year
Overall survival	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	Up to 1 year

Collaborators and Investigators

• Sponsor: iCell Gene Therapeutics
• Collaborators: iCar Bio Therapeutics
• Investigators: Principal Investigator: Peihua Lu, MD, Hebei Yanda Lu Daopei Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: January 16, 2022
• First Submitted That Met QC Criteria: January 16, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: hematologic malignancies; leukemia; CD7; acute lymphoblastic leukemia/lymphoma; CD7CAR
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Neoplasms; Lymphoma; Hematologic Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: ICG170-001

Drug and device information, study documents

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