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

T-cell Lymphoma Clinical Trial

Official title:

Anti-CD7 Universal CAR-T Cells for CD7+ T/NK Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04264078
• Other study ID #: antiCD7-UCAR-T
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 1, 2021
• Est. completion date: June 1, 2023

Study information

• Verified date: June 2021
• Source: Xinqiao Hospital of Chongqing
• Contact: Xi Zhang, MD
• Phone: +8613808310064
• Email: zhangxxi[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia, T-Cell
• T-cell Leukemia
• T-cell Lymphoma

Intervention

Biological:
• CD7 UCAR-T cells
Dose range:1 to 5 ×10^7 cells/Kg, Dose level one: 1×10^7 cells/Kg, Dose level two: 3×10^7 cells/Kg, Dose level three:5 ×10^7 cells/Kg

Drug:
• Fludarabine
30mg/m^2 per day for 6 days
• Cytoxan
600mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline
• Melphalan
50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline

Locations

Country	Name	City	State
China	Department of Hematology, Xinqiao Hospital	ChongQing	Chongqing

Sponsors (13)

Lead Sponsor

Collaborator

Xinqiao Hospital of Chongqing

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Central South University, Fujian Medical University Union Hospital, Gracell Biotechnology Shanghai Co., Ltd., Nanfang Hospital of Southern Medical University, Second Affiliated Hospital of Xi'an Jiaotong University, Tang-Du Hospital, The Affiliated Hospital Of Guizhou Medical University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Kunming Medical College, The General Hospital of Western Theater Command, The Second Affiliated Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the anti-tumor efficiency of anti-CD7 UCAR-T cells	ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value	4 weeks after infusion
Secondary	the long-term efficiency of anti-CD7 UCAR-T cells	ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value	3 and 6 months after infusion