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

Study Overview
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Brief Summary
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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.

Detailed Description
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Primary objectives 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 To measure the efficacy of the CD19CAR T cell infusion combined with allogeneic stem cell transplantation

Official Title
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A Phase I Study of Administrating CD19 Chimeric Antigen Receptor Expressing T Cells Followed by Allogeneic Stem Cell Transplantation in Patients With Refractory CD19+ B-linage Leukemia/Lymphoma

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

Intervention / Treatment
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* Biological: anti-CD19 CAR-T
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD9CAR-T transfer<br>All subjects will receive allogeneic stem cell transplantation after infusion of αCD19-TCRz-CD28 CAR-T | Biological: anti-CD19 CAR-T<br>* Ex vivo-expanded autologous T cells modified to express CD19 CAR<br>Drug: Fludarabine<br>* Patients were given cyclophosphamide 500mg/m2/day on day -4 and fludarabine at 25 mg/m2/day on day -4, day -3, and day -2.<br>Drug: Cyclophosphamide<br>* Patients were given cyclophosphamide 500mg/m2/day on day -4.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - incidence of adverse events defined as dose-limited toxicity | incidence of adverse events defined as dose-limited toxicity | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall complete remission rate | Overall complete remission rate | 1 year | 
| Duration of remission | Duration of remission | 1 year |