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

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

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.

Study Overview

• Status: Recruiting
• Conditions: T-cell Lymphoma; T-cell Leukemia
• Intervention / Treatment: Drug: Fludarabine; Drug: Melphalan; Biological: CD7 UCAR-T cells; Drug: Cytoxan

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xi Zhang, MD; Phone Number: +8613808310064 +8613808310064; Email: zhangxxi@sina.com
• Study Contact Backup: Name: Ruihao Huang; Phone Number: +8618984398751 +8618984398751; Email: 1169731117@qq.com

Study Locations

• China
  • Chongqing
    • ChongQing, Chongqing, China, 400037
      • Recruiting
      • Department of Hematology, Xinqiao Hospital
      • Contact: Xi Zhang, MD; Phone Number: +8613808310064 +8613808310064; Email: zhangxxi@sina.com
      • Contact: Ruihao Huang; Phone Number: +8618984398751 +8618984398751; Email: 1169731117@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: anti-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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (Actual): February 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Neoplasms; Leukemia, T-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Melphalan; Fludarabine
• Other Study ID Numbers: antiCD7-UCAR-T

Drug and device information, study documents

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