Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies

Early Phase 1

• Conditions: T-cell Leukemia; T-cell Lymphoma
• Interventions: Biological: CD7 UCAR-T cells; Drug: Fludarabine; Drug: Cytoxan; Drug: Melphalan

• Registration Number: NCT04264078
• Lead Sponsor: Xinqiao Hospital of Chongqing

Brief Summary

The prognosis of patients with relapsed and/or refractory T-cell hematologic malignancies is poor due to lacking sufficient treatment.Anti-CD(cluster of differentiation antigen)19 CAR(chimeric antigen receptor)-T cell therapies are efficient for patients with B-cell hematologic malignancies. As for T-cell hematologic malignancies, CD7 is a promising target expressed on most malignant T cells. The outcome of CD-7 CAR-T cell therapy pre-clinical experiments is cheerful.however, how to select the functional T cells from the malignant T cells is a challenge. In addition to this, auto-CAR-T cell therapy is not affordable for the majority of patients. Using T cells aphesis from healthy donors edited to avoid rejection of the host as the material of anti-CD7 universal CAR-T cells could be accessible and affordable, which is adapted for patients with CD7+ relapsed and/or refractory T/NK-cell hematologic malignancies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-07
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-11
• Study Start: 2021-03-01
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-21
• Last Update Posted: 2021-06-28
• Primary Completion: 2022-06-01
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher))

  2. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue)）

  3. Hgb ≥ 7.0 (can be transfused)

  4. Life expectancy greater than 12 weeks

  5. Informed consent explained to, understood by and signed by the patient/guardian. Patient/guardian is given a copy of informed consent.

Exclusion Criteria

1. Pregnant or lactating.
2. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
3. Active infection with HIV or HTLV.
4. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
5. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment).
6. CNS abnormalities: Presence of CNS(central nervous system)-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF(cerebrospinal fluid) with ≥ 5 WBC( white blood cell)s per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-CD7 UCAR-T cells	CD7 UCAR-T cells	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD7 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD7 UCAR-T cells	Cytoxan	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD7 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD7 UCAR-T cells	Melphalan	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD7 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD7 UCAR-T cells	Fludarabine	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD7 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated

Primary Outcome Measures

Name	Time	Method
the anti-tumor efficiency of anti-CD7 UCAR-T cells	4 weeks after infusion	ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value

Secondary Outcome Measures

Name	Time	Method
the long-term efficiency of anti-CD7 UCAR-T cells	3 and 6 months after infusion	ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value

Trial Locations

Locations (1)

Department of Hematology, Xinqiao Hospital; 🇨🇳 ChongQing, Chongqing, China