Anti-CD19:TCRζ Chimeric Antigen Receptor-T Cells in the Treatment for CD19+ B Cell Lymphoma

• Sponsor: jiangjingting (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT02992834
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 61
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B Cell	Biological: IL-2 pre-treated CD19 cells; Biological: IL-7/IL-15 pre-treated CD19 cells	Phase 4

Detailed Description

This is a single-centre, randomised, open label Phase I clinical trial of CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma. Following informed consent and registration to the trial, Patients will receive the allogeneic CD19 CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Anti-CD19:TCRζ Chimeric Antigen Receptor-T Cells in the Treatment for Chemotherapy-resistant or Refractory CD19+B Cell Lymphoma:a Double-arm, Single Center, Open-label Clinical Trial
• Study Start Date: Dec 1, 2016
• Anticipated Primary Completion Date: Aug 1, 2020
• Anticipated Study Completion Date: Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IL-2 pre-treated CD19 cells Initial therapy: IL-2 (interleukin,IL)stimulated, CD28-ζ-vector (cluster of differentiation 28,CD28)transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion	Biological: IL-2 pre-treated CD19 cells; IL-2 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
Active Comparator: IL-7/IL-15 pre-treated CD19 cells Initial therapy: IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion	Biological: IL-7/IL-15 pre-treated CD19 cells; IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion

Outcome Measures

Primary Outcome Measures

1. overall survival [5 year]

Secondary Outcome Measures

1. progression-free survival [56 day]

2. Objective Response Rate [56 day]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Enrollment for enough male or female patients with CD19+ hematological malignancies, without regimens for cure (autologous or allogeneic stem cell transplantation), and having a poor prognosis (several months to 2 years) under current optional regimens

1. Age ranges from 18 to 70 years old

2. Expected survival time longer than 12 weeks

3. Performance status score 0-2

4. Pathologically confirmed CD19+ lymphoma (CD19+ follicular lymphoma, Mantle cell lymphoma, diffuse large B cell lymphoma) and meets at least one of follows:

5. having received at least 2-4 cycles of combined chemotherapy (excluding monoclonal antibody monotherapy, such as rituximab) but do not reach a complete response; recurrent disease; not applicable for conventional stem cell transplantation; being partial responsible or stable but not complete responsible after the latest therapy

6. recurrence develops after stem cell transplantation

7. diagnosis confirmed but refusing to receive conventional therapy

8. Creatinine<2.5 mg/dl；

9. alanine aminotransferase/aspartate aminotransferase lower than 3 folds of normal range

10. Bilirubin<2.0 mg/dl；

11. Venous channel available and no contraindications for leukocyte collection

12. Reliable contraception from the beginning to 30 days after discontinuation of therapy

13. Informed consent signed

Exclusion Criteria:

1. Central nerve system invasion with symptoms

2. Other concurrent uncontrolled malignancies

3. Hepatitis B infection or active period of hepatitis C, HIV infection

4. Other uncontrolled diseases hampering the intervention in the study

5. Coronary heart disease, angina, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious cardiovascular or cerebrovascular diseases.

6. Grade 2-3 or uncontrolled hypertension

7. History of uncontrolled mental disease

8. Not suitable for participation judged by researchers

9. Immunosuppressive agents administered due to organ transplantation, not including recent or current inhaled corticosteroid

10. Medical history of mental diseases or abnormities of lab tests might increase the risks of participation in study or drug administration, or interfering the results

11. Screening suggesting transfection efficiency of targeting cells lower than 30% or cell expansion deficiency under CD3/CD28 (cluster of differentiation 3,CD3)stimulation (less than 5 folds)

12. Unstable pulmonary embolism, deep venous thromboembolism or other major arterial/venous thromboembolism events develop in 30 days before the randomization. If anti-coagulation therapy is received, the treatment dose should reach stability before the randomization.

13. Pregnancy or lactation, or pregnancy planned during the study or in 2 months after the study

14. Reliable contraception not accepted during the study or in 2 months after the study. Female subjects are required to provide negative results from serum or urine pregnancy test 48 hours before therapy

15. Systematic active or uncontrolled infection (excluding infection of urinary tract or upper respiratory tract infection) in 14 days before the randomization

16. Informed consent not signed or study rules violated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	First People's Hospital of Changzhou	Changzhou	Jiangsu	China	213003

Sponsors and Collaborators

• jiangjingting

Investigators

• Principal Investigator: Jingting Jiang, Professor, The First People's Hospital of Changzhou

Study Documents (Full-Text)

None provided.

More Information

Publications

• Minagawa K, Jamil MO, Al-Obaidi M, Pereboeva L, Salzman D, Erba HP, Lamb LS, Bhatia R, Mineishi S, Di Stasi A. In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia. PLoS One. 2016 Dec 1;11(12):e0166891. doi: 10.1371/journal.pone.0166891. eCollection 2016. Erratum in: PLoS One. 2017 Feb 15;12 (2):e0172640.
• Rafiq S, Purdon TJ, Daniyan AF, Koneru M, Dao T, Liu C, Scheinberg DA, Brentjens RJ. Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. Leukemia. 2017 Aug;31(8):1788-1797. doi: 10.1038/leu.2016.373. Epub 2016 Dec 7.

• Responsible Party: jiangjingting, Professor, The First People's Hospital of Changzhou
• ClinicalTrials.gov Identifier: NCT02992834
• Other Study ID Numbers: CAAA
• First Posted: Dec 14, 2016
• Last Update Posted: Dec 14, 2016
• Last Verified: Dec 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell

Study Results

No Results Posted as of Dec 14, 2016