Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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 |
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
Drug: Cytoxan
600mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline
Drug: Melphalan
50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline
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Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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- 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))
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CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue))
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Hgb ≥ 7.0 (can be transfused)
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Life expectancy greater than 12 weeks
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Informed consent explained to, understood by and signed by the patient/guardian. Patient/guardian is given a copy of informed consent.
Exclusion Criteria:
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Pregnant or lactating.
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Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
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Active infection with HIV or HTLV.
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Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
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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).
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Department of Hematology, Xinqiao Hospital | ChongQing | Chongqing | China | 400037 |
Sponsors and Collaborators
- Xinqiao Hospital of Chongqing
- Gracell Biotechnology Shanghai Co., Ltd.
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
- The Second Affiliated Hospital of Chongqing Medical University
- The Affiliated Hospital Of Guizhou Medical University
- Central South University
- The First Affiliated Hospital of Kunming Medical College
- The General Hospital of Western Theater Command
- Second Affiliated Hospital of Xi'an Jiaotong University
- Nanfang Hospital of Southern Medical University
- Fujian Medical University Union Hospital
- The First Affiliated Hospital of Anhui Medical University
- Tang-Du Hospital
Investigators
- Principal Investigator: Xi Zhang, MD, Xinqiao Hospital of Chongqing
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- antiCD7-UCAR-T