Clinical Trials /

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

NCT04264078

Description:

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.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
  • Nasal Type Extranodal NK/T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • T-Cell Acute Lymphoblastic Leukemia
  • T-Cell Lymphoblastic Lymphoma
  • T-Cell Non-Hodgkin Lymphoma
  • T-Cell Prolymphocytic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies
  • Official Title: Anti-CD7 Universal CAR-T Cells for CD7+ T/NK Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

Clinical Trial IDs

  • ORG STUDY ID: antiCD7-UCAR-T
  • NCT ID: NCT04264078

Conditions

  • T-cell Leukemia
  • T-cell Lymphoma

Interventions

DrugSynonymsArms
CD7 UCAR-T cellsanti-CD7 UCAR-T cells
Fludarabineanti-CD7 UCAR-T cells
Cytoxananti-CD7 UCAR-T cells
Melphalananti-CD7 UCAR-T cells

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
anti-CD7 UCAR-T cellsExperimentalAfter 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
  • CD7 UCAR-T cells
  • Fludarabine
  • Cytoxan
  • Melphalan

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:the anti-tumor efficiency of anti-CD7 UCAR-T cells
Time Frame:4 weeks after infusion
Safety Issue:
Description:ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value

Secondary Outcome Measures

Measure:the long-term efficiency of anti-CD7 UCAR-T cells
Time Frame:3 and 6 months after infusion
Safety Issue:
Description:ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Xinqiao Hospital of Chongqing

Last Updated

February 7, 2020