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

NCT04264039 | Unknown Early Phase 1

• 1 other identifier: antiCD19-UCAR-T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

B-cell Acute Lymphoblastic Leukemia; B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• the long-term efficiency of anti-CD19 UCAR-T cells

  3 and 6 months after infusion

Study Arms (1)

anti-CD19 UCAR-T cells

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Cytoxan; Drug: Melphalan

Interventions

anti-CD19 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-CD19 UCAR-T cells

Fludarabine DRUG

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

anti-CD19 UCAR-T cells

Cytoxan DRUG

300mg/m\^2 per day for 2 to 6 days determined by tumor burden at baseline

anti-CD19 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-CD19 UCAR-T cells

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Diagnosis of recurrent B-cell acute lymphoblastic leukemia (B-ALL), B-cell acute lymphoblastic lymphoma (B-LLy), or B-non-Hodgkin lymphoma (B-NHL)
• \. CD19-positive tumor (≥20% CD19 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. The 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

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, B-Cell

Interventions

fludarabine; Cyclophosphamide; Melphalan

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

+86 18984398751; 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: April 1, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2022
• Last Updated: February 11, 2020

Record last verified: 2020-02

Locations

CN (1)