Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients

NCT02721407 | Unknown Phase 1 DMC

• 1 other identifier: CD22CART
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to study the feasibility and efficacy of anti-CD22:TCRz:4-1BB chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating recurrent patients with refractory or resistant lymphoma to anti-CD19:TCRz:CD28 CAR-T cells. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the recession of evaluable lesions, the persistence and efficacy of CAR-T cells are still restricted by the "target" selection. Previous clinical studies largely utilized CD19 for the in vivo targeting of CAR-T cells, which preferentially become refractory or resistant due to the heterogeneity of lymphoma. This clinical investigation is to test a hypothesis whether anti-CD22 CAR-T cells work more effective in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells.

Conditions

Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III/IV Adult Diffuse Large Cell Lymphoma; Stage III/IV Follicular Lymphoma; Stage III/IV Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

  4 Weeks

Secondary Outcomes (3)

• Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm

  8 Weeks

• Duration of CAR-positive T cells in circulation

  6 months

• Total number of CAR-positive T cells infiltrated into lymphoma tissue

  6 months

Study Arms (1)

Anti-CD22 CAR-T

EXPERIMENTAL

Administrated with CD22.CAR-T cells on day 0,1,2 in the lympho-depleted patients

Drug: Retroviral vector-transduced autologous T cells to express CD22-specific CARs

Interventions

Retroviral vector-transduced autologous T cells to express CD22-specific CARs DRUG

Anti-CD22 CAR-T

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Years to 70 Years, Male and female;
• Expected survival \> 12 weeks;
• Performance score 0-2;
• Histologically confirmed as CD19-positive lymphoma 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.
• Refractory ot resistant to prior anti-CD19 CAR-Ts
• At least one evaluable CD22-positive recurrent lesion, confirmed by two independent pathologist.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Xuzhou Medical University: collaborator

Study Sites (1)

Department of Oncology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Cancer

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: March 29, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: March 10, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)