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

Anti-CD19 Universal CAR-T Cells for CD19+ B Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

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.

Study Overview

• Status: Unknown
• Conditions: B-cell Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: anti-CD19 UCAR-T cells; Drug: Fludarabine; Drug: Cytoxan; Drug: Melphalan

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

Contacts and Locations

Study Locations

• China
  • Chongqing
    • ChongQing, Chongqing, China, 400037
      • Department of Hematology, Xinqiao Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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-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

Biological: anti-CD19 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; 300mg/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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the long-term efficiency of anti-CD19 UCAR-T cells	ratio of bone marrow blast cells and/or the measurable lesion size and strandralized 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 (Anticipated): April 1, 2020
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2022

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): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

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; Precursor Cell Lymphoblastic Leukemia-Lymphoma; 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: antiCD19-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
• product manufactured in and exported from the U.S.: No