ThisCART19A Bridging to alloHSCT for R/R B-ALL

Refractory Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic Anti CD19 CAR-T Bridging to Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05679687
• Other study ID #: SZ4602
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2022
• Est. completion date: November 30, 2025

Study information

• Verified date: December 2022
• Source: The First Affiliated Hospital of Soochow University
• Contact: Jia Chen, M.D., Ph.D.
• Phone: +86-512-67781856
• Email: drchenjia[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1, open-label study to assess the efficacy, safety and pharmacokinetics of ThisCART19A (Allogeneic Anti CD19 CAR-T) bridging to HSCT in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL).

Description:

This is a phase 1, single-center, nonrandomized, open-label, dose-escalation study to evaluate the efficacy, safety and pharmacokinetics of ThisCART19A bridging to HSCT in patients with CD19 positive r/r B-ALL and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile. Before initiating ThisCART19A infusion, subjects will be administered lymphodepletion chemotherapy composed of fludarabine、cyclophosphamide and VP-16. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of ThisCART19A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of ThisCART19A will be followed up to 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure.

2. No gender limitation, 14 years = age = 65 years.

3. Intention to HSCT therapy.

4. Meeting the diagnostic criteria of relapsed or refractory B-ALL. Relapsed B-ALL:

Reappearance of blasts in the blood or bone marrow (>5%) or in any extramedullary site after a CR. Refractory B-ALL: Failure to achieve CR or CRi at the end of induction therapy (General refers to a 4-week regimen or a Hyper-CVAD regimen); Subjects with Ph+ disease are eligible if they are intolerant to TKI therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs.

5. Life expectancy = 8 weeks at the time of enrollment.

6. Eastern Cooperative Oncology Group performance status score of 0 or 1.

7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function:

1. Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator.

2. Creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula;

3. ALT and AST = 5 × ULN (the upper limit of normal), total bilirubin = 2×ULN. (Subjects with Gilbert syndrome or liver involvement may be included if their total bilirubin is = 3 × ULN.)

4. Oxygen saturation (SaO2) = 92% on room air.

5. Cardiac function:left ventricular ejection fraction (LVEF) = 40% assessed by echocardiography.

8. CD19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening.

Exclusion Criteria:

1. Allergic to preconditioning measures.

2. History of allogeneic HSCT.

3. Other malignancies apart from B-cell malignancies within 5 years prior to screening. (Subjects with cured skin squamous carcinoma, basal cell carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be enrolled.)

4. Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.)

5. Pulmonary embolism within 3 months prior to enrollment.

6. Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment.

7. Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging;

8. Active hepatitis B virus (defined as serum HBV-DNA = 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Subjects with HBV-DNA < 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.)

9. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (Subjects vaccinated with SARS-COV19 vaccine or inactivated, live/non-live adjuvant vaccines can be enrolled.)

10. Female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after CAR-T cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after CAR-T cell infusion.

11. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Related Conditions & MeSH terms

• CAR
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Refractory Acute Lymphoblastic Leukemia
• Relapsed Adult ALL

Intervention

Drug:
• Treatment
In this study, allogeneic anti-CD19 CAR T cells (ThisCART19A) infusion is used as a bridge therapy to hematopoietic stem cell transplantation to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. Lymphodepletion conditioning before CAR T cell infusion consists of fludarabine, CTX and VP-16.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Fundamenta Therapeutics, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	Overall response rate	4 week
Primary	MRD Negativity	MRD Negativity is assessed utilizing multicolor flow cytometry to detect leukemia cells with a sensitivity of 10^ (-4).	4 week
Secondary	CR	Complete response	2 year
Secondary	CRi	CR with incomplete hematologic recovery	2 year
Secondary	CRh	CR with partial hematological recovery	2 year
Secondary	BFBM	Blast-free hypoplastic or aplastic bone marrow	2 year
Secondary	PR	Partial response	2 year
Secondary	DOR	Duration of response	2 year
Secondary	LFS	Leukemia-free survival	2 year
Secondary	OS	Overall survival	2 year