Clinical trial NCT04264039: Anti-CD19 U-CAR-T Cell Therapy for B Cell Hematologic Malignancies
Official title: Anti-CD19 Universal CAR-T Cells for CD19+ B Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: B-cell Acute Lymphoblastic Leukemia
B-cell Lymphoma
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: Gracell Biotechnologies (Shanghai) Co., Ltd.
name: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: The Second Affiliated Hospital of Chongqing Medical University
name: The Affiliated Hospital Of Guizhou Medical University
name: Central South University
name: First Affiliated Hospital of Kunming Medical University
name: The General Hospital of Western Theater Command
name: Second Affiliated Hospital of Xi'an Jiaotong University
name: Nanfang Hospital, Southern Medical University
name: Fujian Medical University Union Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: Tang-Du Hospital
First posted: 2020-02-11
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: the anti-tumor efficiency of anti-CD19 UCAR-T cells
timeFrame: 4 weeks after infusion
Secondary outcomes:
measure: the long-term efficiency of anti-CD19 UCAR-T cells
timeFrame: 3 and 6 months after infusion
Other outcomes:
Locations:
city: ChongQing
country: China
facility: Department of Hematology, Xinqiao Hospital
state: Chongqing
Study officials:
affiliation: Xinqiao Hospital of Chongqing
name: Xi Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: