Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 (ThisCART19A) in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy in china.

Study Overview

• Status: Not yet recruiting
• Conditions: Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: ThisCART19A; Drug: Fludarabine Pill; Drug: VP-16 Protocol

Detailed Description

This is a phase 1, single-center, nonrandomized, open-label, dose-escalation and dose expansion study to evaluate the safety and efficacy of ThisCART19A in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Keshu zhou, Dr.; Phone Number: +86-13674902391; Email: drzhouks77@163.com
• Study Contact Backup: Name: Jun Li, Ph.D; Phone Number: +86-18662604088; Email: jli@ctigen.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma；
2. No gender limitation, Age 14 years to 75 years (both upper and lower limits included)；
3. Failing to autologous CAR-T therapy；
4. Should be confirmed Cluster of differentiation(CD)19 positive；
5. The expected survival time is ≥12 weeks;
6. ECOG score 0-1;
7. Measurable or detectble disease at time of enrollment.
8. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function；

Exclusion Criteria:

1. Allergic to preconditioning measures；
2. Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited；
3. Uncontrollable bacterial, fungal and viral infection during screening；
4. Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
5. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment；
6. The presence of central nervous system involvement；
7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment；
8. Had big lesion(single lesion diameter ≥10 cm)；
9. Receive allogeneic hematopoietic stem cell transplantation less than 100 days；
10. Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included)；
11. Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion；
12. Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ThisCART19A cells infusion; In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.	Drug: Cyclophosphamide; Cyclophosphamide is used for lymphodepletion.; Drug: ThisCART19A; ThisCART19A is a new type CAR-T therapy for patients with r/r B Cell Malignancy .; Drug: Fludarabine Pill; Fludarabine is used for lymphodepletion.; Drug: VP-16 Protocol; VP-16 is used for lymphodepletion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limited toxicity(DLT) observation in patient with B Cell Malignancy in each dose level during dose escalation stage	DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.	28 days
Objective Response Rate within 3 months during dose expansion stage	For Acute Lymphoblastic Leukemia (ALL), Objective response rate(ORR) is the percentage of patients who achieve Complete Response (CR) or Complete Response With Incomplete Hematologic Recovery (CRi); for lymphoma, ORR is the incidence of either a complete response (CR) or a partial response (PR).	3 months
Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage	MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response(DOR) during dose escalation stage and expansion stage	DOR was defined as the time from first CR/CRi or PR to relapse or any death in the absence of documented relapse.	24 months
Relapse-free Survival (RFS)	RFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse or death from any cause.	24 months
Event-free Survival (EFS)	EFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse, progression, genetic relapse or death from any cause.	24 months
Overall Survival (OS)	OS is defined as the time from the date of ThisCART19A infusion to the date of death from any cause.	24 months

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: Fundamenta Therapeutics, Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Estimate): December 7, 2022

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: ThisCART19A （FT400-011）

Drug and device information, study documents

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