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

NCT ID: NCT03110640

Last Updated: 2019-11-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-01
• Study Completion Date: 2021-09-30

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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD9CAR-T transfer

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

Group Type: EXPERIMENTAL

anti-CD19 CAR-T

Intervention Type: BIOLOGICAL

Ex vivo-expanded autologous T cells modified to express CD19 CAR

Fludarabine

Intervention Type: DRUG

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.

Cyclophosphamide

Intervention Type: DRUG

Patients were given cyclophosphamide 500mg/m2/day on day -4.

Interventions

anti-CD19 CAR-T

Ex vivo-expanded autologous T cells modified to express CD19 CAR

Intervention Type: BIOLOGICAL

Fludarabine

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.

Intervention Type: DRUG

Cyclophosphamide

Patients were given cyclophosphamide 500mg/m2/day on day -4.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hrain Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Kang YU

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kang Yu, M.D.

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Wenzhou Medical University

Locations

The First Affilicated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Kang Yu, M.D.

Role: CONTACT

yukang62@126.com

55578037

Facility Contacts

Kang Yu, M.D

Role: primary

yukang62@126.com

55578037

References

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.

Reference Type: DERIVED

PMID: 34935483 (View on PubMed)

Other Identifiers

20170316

Identifier Type: -

Identifier Source: org_study_id