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

NCT04264078 | Unknown Early Phase 1

• 1 other identifier: antiCD7-UCAR-T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

T-cell Leukemia; T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• the long-term efficiency of anti-CD7 UCAR-T cells

  3 and 6 months after infusion

Study Arms (1)

anti-CD7 UCAR-T cells

EXPERIMENTAL

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

Biological: CD7 UCAR-T cells; Drug: Fludarabine; Drug: Cytoxan; Drug: Melphalan

Interventions

CD7 UCAR-T cells BIOLOGICAL

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

anti-CD7 UCAR-T cells

Fludarabine DRUG

30mg/m\^2 per day for 6 days

anti-CD7 UCAR-T cells

Cytoxan DRUG

600mg/m\^2 per day for 2 to 6 days determined by tumor burden at baseline

anti-CD7 UCAR-T cells

Melphalan DRUG

50 to 70 mg/m\^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline

anti-CD7 UCAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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))
• \. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue)）
• \. Hgb ≥ 7.0 (can be transfused)
• \. Life expectancy greater than 12 weeks
• \. Informed consent explained to, understood by and signed by the patient/guardian. Patient/guardian is given a copy of informed consent.

You may not qualify if:

• Pregnant or lactating.
• Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
• Active infection with HIV or HTLV.
• Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
• 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).
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

RECRUITING

MeSH Terms

Conditions

Leukemia, T-Cell; Lymphoma, T-Cell

Interventions

fludarabine; Cyclophosphamide; Melphalan

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Xi Zhang, MD

  Xinqiao Hospital of Chongqing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xi Zhang, MD

CONTACT

+8613808310064; zhangxxi@sina.com

Ruihao Huang

CONTACT

+8618984398751; 1169731117@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chef of Hematology Department

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: March 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: June 28, 2021

Record last verified: 2021-06

Locations

CN (1)