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

March 8, 2017 updated by: Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

A Phase I Study of Anti-CD22:TCRz:4-1BB T-cells in Patient With CD22-Positive Recurrent Lymphoma That is Resistant or Refractory to Prior Anti-CD22:TCRz:CD28 Immunotherapy

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Primary Objectives

  1. To determine the safety of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells
  2. To determine in vivo dynamics and persistency of CD22.CAR-T cells.

Secondary Objectives

  1. To determine the feasibility of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells
  2. To determine in vivo dynamics and persistency of CD22.CAR-T cells.
  3. To assess the intratumoral infiltration of CD22.CAR-T cells.
  4. To correlate the subsets and differentiation of CD22.CAR-T cells to observed anti-tumor efficacy

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Chongqing
      • ChongQing, Chongqing, China, 400037
        • Recruiting
        • Department of Oncology, Xinqiao Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1.18 Years to 70 Years, Male and female;

2.Expected survival > 12 weeks;

3.Performance score 0-2;

4.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

    5.Creatinine < 2.5 mg/dl;

    6.ALT/AST < 3x normal;

    7.Bilirubin < 2.0 mg/dl;

    8.Adequate venous access for apheresis, and no other contraindications for leukapheresis;

    9.Take contraceptive measures before recruit to this trial;

    10.Written voluntary informed consent is given.

    11.Refractory ot resistant to prior anti-CD19 CAR-Ts

    12.At least one evaluable CD22-positive recurrent lesion, confirmed by two independent pathologist.

Exclusion Criteria:

  1. Patients with symptoms of central nervous system
  2. Accompanied by other malignant tumor
  3. Active hepatitis B or C, HIV infection
  4. Any other diseases could affect the outcome of this trial
  5. Suffering severe cardiovascular or respiratory disease
  6. Poorly controlled hypertension
  7. A history of mental illness and poorly controlled
  8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
  9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
  10. Reaching a steady dose if receiving anticoagulant therapy before assignment
  11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  12. Pregnant or lactating women
  13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-CD22 CAR-T
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Time Frame: 4 Weeks
4 Weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Time Frame: 8 Weeks
8 Weeks
Duration of CAR-positive T cells in circulation
Time Frame: 6 months
6 months
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xinqiao Hospital of Chongqing

Collaborators

Xuzhou Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2016

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

March 23, 2016

First Submitted That Met QC Criteria

March 23, 2016

First Posted (Estimate)

March 29, 2016

Study Record Updates

Last Update Posted (Actual)

March 10, 2017

Last Update Submitted That Met QC Criteria

March 8, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CD22CART

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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