Combination Transfer of αCD19-TCRz-41BB and αCD22-TCRz-41BB CAR-T Cells for B-cell Hematologic Malignancy

October 11, 2016 updated by: Jiang Cao, Xuzhou Medical University

A Phase I/II Study of Combination Transfer of αCD19-TCRz-41BB and αCD22-TCRz-41BB Chimeric Antigen Receptor T-Cells in Patients With Refractory or Recurrent CD19/22+ B-lineage Leukemia/Lymphoma

Clinical study of CD19 CAR-T in the treatment of blood and lymphatic system tumor has been achieved a breakthrough. The main solution in clinical research is to use CD19 CAR-T infusion alone. Because of the heterogeneity of the tumor, the patient often carries tumor cells with CD19 deficient but other positive target antigens (such as CD22). Specifically removal of CD19 positive tumor cells in CAR-T treatment, CD19 negative tumor cells or tumor cells which carry other target antigens would amplify with extra free space released at the same time, resulting in the relapse of tumors of heterogeneities. In order to effectively control the recurrence, CAR-T treatment scheme specific for several target antigens was presented and verified. However treatment with the sequential infusion of different target specific CAR-T cells, the window period between two times infusions may be the opportunity for the tumor recurrence of heterogeneity; and bispecific CAR-T has also been reported only one CAR can be fully functioned. In order to avoid these problems, this topic puts forward for the first time in the international with a treatment scheme of an equal amount of infusion of CD19-41BB and CD22-41BB two Car-T in the treatment of refractory hematologic malignancies. We expect the treatment is more effective in eliminating tumor burden, and also can inhibit the recurrence of tumor heterogeneity at the same time.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

To determine:

Primary Outcome Measure:

  • Safety (incidence of adverse events defined as dose-limited toxicity)

Secondary Outcome Measures:

  • Survival of CAR T cells in circulation measured by flow cytometry and qPCR
  • Overall complete remission rate
  • Tissue infiltration of transferred CAR-T cells
  • In vitro killing potential of infiltrated CAR-T cells
  • Phenotype of infused CAR-T cells

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • 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

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:

  • 18 Years to 70 Years, Male and female
  • Expected survival > 12 weeks
  • Performance score 0-2
  • Histologically confirmed as CD19/22-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 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: Mixed CAR-T Transfer
All subjects will be infused with αCD19-TCRz-41BB and αCD22-TCRz-41BB CAR-T cells in equal number
Biological: Mixed CAR-T Transfer
All subjects will be infused with αCD19-TCRz-41BB and αCD22-TCRz-41BB CAR-T cells in equal number

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety (incidence of adverse events defined as dose-limited toxicity)
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall complete remission rate
Time Frame: 8 weeks
8 weeks
Survival of CAR T cells in circulation measured by flow cytometry and qPCR
Time Frame: 1 years
1 years
Tissue infiltration of transferred CAR-T cells
Time Frame: 1 years
1 years
In vitro killing potential of infiltrated CAR-T cells
Time Frame: 1 years
1 years
Phenotype of infused CAR-T cells
Time Frame: 1 years
1 years

Collaborators and Investigators

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

Sponsor

Xuzhou Medical University

Investigators

  • Principal Investigator: Jiang Cao, Doctor, 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

September 1, 2016

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

September 13, 2016

First Submitted That Met QC Criteria

September 15, 2016

First Posted (Estimate)

September 16, 2016

Study Record Updates

Last Update Posted (Estimate)

October 12, 2016

Last Update Submitted That Met QC Criteria

October 11, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • XZCJ20160001

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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