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

Phase 1

• Conditions: Hematopoietic/Lymphoid Cancer; Refractory Chronic Lymphocytic Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Chronic Lymphocytic Leukemia
• Interventions: Biological: anti-CD19 CAR-T; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT03110640
• Lead Sponsor: First Affiliated Hospital of Wenzhou Medical University

Brief Summary

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

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

Study Timeline

• Study Start: 2016-10-01
• Study First Submitted: 2017-04-06
• Study First Submitted QC: 2017-04-11
• Study First Posted: 2017-04-12
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-25
• Last Update Posted: 2019-11-27
• Primary Completion: 2020-06
• Study Completion: 2021-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD9CAR-T transfer	anti-CD19 CAR-T	All subjects will receive allogeneic stem cell transplantation after infusion of αCD19-TCRz-CD28 CAR-T
CD9CAR-T transfer	Fludarabine	All subjects will receive allogeneic stem cell transplantation after infusion of αCD19-TCRz-CD28 CAR-T
CD9CAR-T transfer	Cyclophosphamide	All subjects will receive allogeneic stem cell transplantation after infusion of αCD19-TCRz-CD28 CAR-T

Primary Outcome Measures

Name	Time	Method
Safety - incidence of adverse events defined as dose-limited toxicity	180 days	incidence of adverse events defined as dose-limited toxicity

Secondary Outcome Measures

Name	Time	Method
Duration of remission	1 year	Duration of remission
Overall complete remission rate	1 year	Overall complete remission rate

Trial Locations

Locations (1)

The First Affilicated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China