Immunotherapy With CD22 CAR T-cells for B-Cell Lymphoma, ALL and CLL

Phase I Study of T Cells Expressing an Anti-CD22 Chimeric Receptor in Children and Young Adults With B Cell Malignancies

This study aims to evaluate the safety, efficacy and duration of response of CD22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in patients with high risk, relapsed CD22+ haematological malignancies.

Study Overview

• Status: Unknown
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: :Anti-CD22-CAR

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD22 Chimeric Antigen Receptor (CAR) T-cells (CD22 CAR T-cells) in patients with high risk, relapsed CD22+ haematological malignancies (Leukemia and lymphoma). Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD22 CAR Tcells. Patients will receive the CD22CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD22 CAR T-cells in patients with high risk relapsed CD22+ malignancies

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 66 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphoblastic leukemia(CLL) and non-hodgkin lymphoma.
2. KPS>60.
3. Life expectancy>3 months.
4. Gender unlimited, age from 2 years to 70 years.
5. CD22 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 30% by flow cytometry.
6. Patients who have failed at least one line of a standard treatment.
7. No serious mental disorder.
8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L).
9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
10. No other tumors.
11. Patients volunteer to participate in the research.
12. Patients with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to

Exclusion Criteria:

1. KPS<50.
2. Patients are allergic to cytokines.
3. Central nervous system leukemia within 28 days.
4. Uncontrolled active infection.
5. Acute or chronic GVHD.
6. Treated with T cell inhibitor.
7. Pregnancy and nursing females.
8. HIV/HBV/HCV Infection.
9. Other situations we think improper for the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental:1; Acute lymphoblastic leukemia treated with chimeric antigen receptor modified T cells(Anti-CD22-CAR) targeting CD22.	Biological: :Anti-CD22-CAR; Cells extracted, followed by induction chemotherapy before CD22-CAR infusion (dose escalation.)
Experimental: experimental:2; Chronic lymphoblastic leukemia with chimeric antigen receptor modified T cells(Anti-CD22-CAR) targeting CD22.	Biological: :Anti-CD22-CAR; Cells extracted, followed by induction chemotherapy before CD22-CAR infusion (dose escalation.)
Experimental: experimental:3; Non-hodgkin lymphoma treated with chimeric antigen receptor modified T cells(Anti-CD22-CAR) targeting CD22.	Biological: :Anti-CD22-CAR; Cells extracted, followed by induction chemotherapy before CD22-CAR infusion (dose escalation.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumor Effects	Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.	Every 3 months post treatment up to 24 months
Adverse events of each patient	Determine the toxicity profile of the CD22 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0	3 years
Survival time of Anti-CD22 CAR T cells in vivo	To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.	3 years
Maximum tolerated dose (MTD) of CD22 targeted CAR T cells.	Maximum tolerated dose (MTD) of CD22 targeted CAR T cells.	4 weeks

Collaborators and Investigators

• Sponsor: Kecellitics Biotech Company Ltd
• Collaborators: Hebei Yanda Ludaopei Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: lymphoma; CAR-T; Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: Kece-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No