Clinical trial NCT03110640: Anti-CD19 CAR T Infusion Combined With Allogeneic Stem Cell Transplantation for B-cell Leukemia/Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Hematopoietic/Lymphoid Cancer
Refractory Chronic Lymphocytic Leukemia
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
Collaborators: name: Hrain Biotechnology Co., Ltd.
name: Second Affiliated Hospital of Nanchang University
First posted: 2017-04-12
Enrollment: 20
Sex: ALL
Minimum age (years): 5
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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Safety - incidence of adverse events defined as dose-limited toxicity
timeFrame: 180 days
Secondary outcomes:
measure: Overall complete remission rate
timeFrame: 1 year
measure: Duration of remission
timeFrame: 1 year
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: The First Affilicated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: Kang Yu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dong R, Jiang S, Chen Y, Ma Y, Sun L, Xing C, Zhang S, Yu K. Prognostic Significance of Cytokine Release Syndrome in B Cell Hematological Malignancies Patients After Chimeric Antigen Receptor T Cell Therapy. J Interferon Cytokine Res. 2021 Dec;41(12):469-476. doi: 10.1089/jir.2021.0057.