Anti-CD19 CAR T Infusion Combined With Allogeneic Stem Cell Transplantation for B-cell Leukemia/Lymphoma

Wenzhou Medical University

Status and phase: Unknown; Phase 1

Conditions: Refractory Chronic Lymphocytic Leukemia; Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Chronic Lymphocytic Leukemia; B-cell Adult Acute Lymphoblastic Leukemia

Treatments: Biological: anti-CD19 CAR-T; Drug: Cyclophosphamide; Drug: Fludarabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03110640

20170316

Details and patient eligibility

About

This is a single-arm open-label phase I study to determine the effect of CD19- CAR-T Cells infusion followed by allogeneic stem cell transplantation in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma.

Full description

Primary objectives

1. To determine the safety and feasibility of allogeneic stem cell transplantation combined with adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma Secondary objectives
2. To measure the efficacy of the CD19CAR T cell infusion combined with allogeneic stem cell transplantation

Enrollment: 20 estimated patients

Sex: All

Ages: 5 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 5 Years to 70 Years, Male and female;
• Expected survival > 12 weeks;
• Performance score 0-2;
• Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions; Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment; Disease recurrence after stem cell transplantation; Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
• Creatinine < 2.5 mg/dl;
• ALT/AST < 3x normal;
• Bilirubin < 2.0 mg/dl;
• Adequate venous access for apheresis, and no other contraindications for leukapheresis;
• Take contraceptive measures before recruit to this trial;
• Written voluntary informed consent is given.

Exclusion criteria

• Patients with symptoms of central nervous system
• Accompanied by other malignant tumor
• Active hepatitis B or C, HIV infection
• Any other diseases could affect the outcome of this trial
• Suffering severe cardiovascular or respiratory disease
• Poorly controlled hypertension
• A history of mental illness and poorly controlled
• Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
• Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
• Reaching a steady dose if receiving anticoagulant therapy before assignment
• Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
• Pregnant or lactating women
• Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

CD9CAR-T transfer

Experimental group

Description:

All subjects will receive allogeneic stem cell transplantation after infusion of αCD19-TCRz-CD28 CAR-T

Treatment:

Drug: Fludarabine

Biological: anti-CD19 CAR-T

Drug: Cyclophosphamide