Anti-CD19 U-CAR-T Cell Therapy for B Cell Hematologic Malignancies

Early Phase 1

• Conditions: B-cell Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Interventions: Biological: anti-CD19 UCAR-T cells; Drug: Fludarabine; Drug: Cytoxan; Drug: Melphalan

• Registration Number: NCT04264039
• Lead Sponsor: Xinqiao Hospital of Chongqing

Brief Summary

The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, based on open clinical trials, using patients' T cells might encounter the failure of apheresis available T cells, even if successful, the time needed for the manufacture could also cause the irreversible disease progress. Furthermore, the cost of auto-CAR-T cells is not affordable for most patients. So to provide an accessible and affordable anti-CD19 CAR-T cell therapy for patients with B-cell hematologic malignancies, we launch such a trial that using the edited T cells from healthy donors to manufacture universal CAR-T cells and adapt it in patients with CD19+ B-cell leukemia or lymphoma.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-02
• Study First Submitted: 2020-02-07
• Study First Submitted QC: 2020-02-07
• Last Update Submitted: 2020-02-07
• Study First Posted: 2020-02-11
• Last Update Posted: 2020-02-11
• Study Start: 2020-04-01
• Primary Completion: 2021-04-01
• Study Completion: 2022-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 1. Diagnosis of recurrent B-cell acute lymphoblastic leukemia (B-ALL), B-cell acute lymphoblastic lymphoma (B-LLy), or B-non-Hodgkin lymphoma (B-NHL)

  2. CD19-positive tumor (≥20% CD19 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. The 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-CD19 UCAR-T cells	anti-CD19 UCAR-T cells	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD19 UCAR-T cells	Cytoxan	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD19 UCAR-T cells	Melphalan	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated
anti-CD19 UCAR-T cells	Fludarabine	After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10\^7 cells/Kg will be evaluated

Primary Outcome Measures

Name	Time	Method
the anti-tumor efficiency of anti-CD19 UCAR-T cells	4 weeks after infusion	ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Secondary Outcome Measures

Name	Time	Method
the long-term efficiency of anti-CD19 UCAR-T cells	3 and 6 months after infusion	ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Trial Locations

Locations (1)

Department of Hematology, Xinqiao Hospital; 🇨🇳 ChongQing, Chongqing, China