Safety and Efficacy of ThisCART19A Bridging Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia

NCT05576181 | Unknown Phase 1

• 1 other identifier: ThisCART19 FT400-007
• Study Type: interventional
• Target: 19
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) Bridging Hematopoietic Stem Cell Transplantation in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL).

Conditions

Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited

Outcome Measures

Primary Outcomes (2)

• Dose limited toxicity(DLT) observation in patient with B-ALL in each dose level during dose escalation and dose expansion stage

  DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.

  28 days

• Overall Complete Response (OCR) Rate (Complete Remission [CR]+ Complete Remission With Incomplete Hematologic Recovery [CRi]) within 3 months

  OCR rate within 3 months: percentage of participants achieving CR+CRi within 3 months after CAR-T cell infusion.

  3 months

Secondary Outcomes (5)

• Minimum Residual Disease (MRD) Negative Remission Rate

  3 months

• Duration of response(DOR) during dose escalation stage and expansion stage

  24 months

• RFS (Relapse-free Survival)

  24 months

• EFS (Event-free Survival)

  24 months

• OS (Overall Survival)

  24 months

Study Arms (1)

ThisCART19A cells infusion and HSCT

EXPERIMENTAL

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. After patients achieve MRD- remissions through ThisCART19A, they will subsequently receive hematological stem cell transplantations.

Drug: ThisCART19A; Drug: Fludarabine Oral Tablet; Drug: Cyclophosphamide; Drug: VP-16; Procedure: HSCT

Interventions

ThisCART19A DRUG

ThisCART19A is a new type CAR-T therapy for patients with r/r B-ALL.

ThisCART19A cells infusion and HSCT

Fludarabine Oral Tablet DRUG

Fludarabine is used for lymphodepletion.

ThisCART19A cells infusion and HSCT

Cyclophosphamide DRUG

Cyclophosphamide is used for lymphodepletion.

ThisCART19A cells infusion and HSCT

VP-16 DRUG

VP-16 is used for lymphodepletion.

Also known as: etoposide

ThisCART19A cells infusion and HSCT

HSCT PROCEDURE

Hematological stem cell transplantation

ThisCART19A cells infusion and HSCT

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
• Patients diagnosed with B-ALL;
• No gender limitation, Age 14 years to 75 years (both upper and lower limits included);
• Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment; The following factors can coexist:
• Failure to prepare autologous CAR-T (definition: too few autologous lymphocytes \[200/ML\] or cannot meet the release standard);
• Experienced treatment with auto car-T/berintoomumab/ CD22 antibody conjugation drugs;
• ≥100 days after hematopoietic stem cell transplantation;
• High-risk patients (High risk was defined as a high white blood cell count ≥30×109/L at diagnosis or with poor cytogenetic prognosis);
• Hypodiploid (\<44 chromosomes);
• KMT2A rearrangement: t (4;11) or otherwise;
• t (v; 14q32) /IgH
• t (9; 22) (q34; q11.2) or BCR-ABL1
• Complex karyotype (≥5 chromosomal abnormalities);
• BCR-ABL1-like (Ph-like) ALL;
• JAK-STAT (CRLF2r, EPORr, JAK1/2/3r, TYK2r, mutations of SH2B3, IL7r, Jak1/2/3);

You may not qualify if:

• Allergic to preconditioning measures;
• Diagnosis of chronic myelogenous leukemia lymphoid blast crisis;
• Isolated extramedullary relapse;
• Presence of CNS-3 disease or CNS-2 disease with neurological changes;
• Imaging confirmed the presence of central nervous system involvement;
• Severe CNS disorders such as a history of frequent epileptic seizures;
• 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.
• Uncontrollable bacterial, fungal and viral infection during screening;
• Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
• Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment;
• Radiation therapy within 2 weeks prior to lymphodepletion chemotherapy (\>30% bone marrow exposure);
• 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;
• Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) ;
• 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;
• Any ineligibility conditions considered by the investigator that may increase the risk of the subject or interfere with the results of the study.

Sponsors & Collaborators

• Fundamenta Therapeutics, Ltd.: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator

MeSH Terms

Interventions

fludarabine; Cyclophosphamide; Etoposide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Yongping Song, Ph.D

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Li, Ph.D

CONTACT

+86-18662604088; jli@ctigen.com

Yongping Song, Ph.D

CONTACT

+86-13521186987; songyongping@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: October 12, 2022
• Study Start: October 15, 2022
• Primary Completion: January 22, 2025
• Study Completion: July 22, 2025
• Last Updated: October 12, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share