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

Hematopoietic/Lymphoid Cancer Clinical Trial

Official title:

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 Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02903810
• Other study ID #: XZCJ20160001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 13, 2016
• Last updated: October 11, 2016
• Start date: September 2016
• Est. completion date: December 2019

Study information

• Verified date: October 2016
• Source: Xuzhou Medical University
• Contact: Jiang Cao, Doctor
• Phone: 138-5243-2263
• Email: CaoJiangClinicalTrial[@]outlook.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematopoietic/Lymphoid Cancer

Intervention

Biological:
• Mixed CAR-T Transfer
All subjects will be infused with aCD19-TCRz-41BB and aCD22-TCRz-41BB CAR-T cells in equal number

Locations

Country	Name	City	State
China	XuZhou Medical University	XuZhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Xuzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (incidence of adverse events defined as dose-limited toxicity)		30 days	Yes
Secondary	Survival of CAR T cells in circulation measured by flow cytometry and qPCR		1 years	No
Secondary	Overall complete remission rate		8 weeks	No
Secondary	Tissue infiltration of transferred CAR-T cells		1 years	No
Secondary	In vitro killing potential of infiltrated CAR-T cells		1 years	No
Secondary	Phenotype of infused CAR-T cells		1 years	No