RPM CD19-mbIL15-CAR-T Cells in Patient With Advanced Lymphoid Malignancies

NCT04844086 | Terminated Phase 1

• 1 other identifier: Eden 2020-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label Phase 1 study to determine the feasibility, safety, and the recommended maximum tolerated Dose (MTD) of a single infusion of RPM CD19 mbIL15 CAR-T cells for adult patients. Approximately 24 subjects will be enrolled and it is anticipated approximately 16 subjects will be infused at the varied doses of T cells.

Conditions

B-cell Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma, Relapsed; Non-Hodgkin's Lymphoma Refractory; Primary Mediastinal Large B Cell Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; High-grade B-cell Lymphoma

Keywords

CD19 specific CAR; Autologous

Outcome Measures

Primary Outcomes (1)

• Maximun Tolerated Dose (MTD) of the RPM CD19- mbIL15-CAR-T

  MTD is the highest dose at which no more than 1 of 6 patients experiences a dose limiting toxicity.

  within 4 weeks after infusion

Secondary Outcomes (11)

• Feasibility of the product manufacturing process

  day 0 to month 12

• Adverse events related to treatment

  day 0 to month 12

• Persistence of infused T cells

  day 0 to month 12

• Safety Switch Function

  day 0 to month 12

• Immunogenicity

  day 0 to month 12

Study Arms (1)

Infusion RPM CD19-mbIL15-CAR-T cell

EXPERIMENTAL

In this study, anti-CD19 autologous chimeric antigen receptor T-cells infusion produced by rapid personalized manufacture are used to treat patients with relapsed/refractory Advanced Lymphoid Malignancies. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to RPM CD19-mbIL15-CAR-T cell infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Biological: RPM CD19-mbIL15-CAR-T cells

Interventions

RPM CD19-mbIL15-CAR-T cells BIOLOGICAL

Single dose of RPM CD19-mbIL15-CAR-T cells will be infused, and a standard "3+3" design will be applied. Drug: Fludarabine Fludarabine is used for lymphodepletion. Drug: Cyclophosphamide Cyclophosphamide is used for lymphodepletion

Infusion RPM CD19-mbIL15-CAR-T cell

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject may participate in the study if all the following criteria is met:
• Patients with CD19+ malignancies that are refractory to or relapsed after current standard treatment (including allogeneic or autologous HSCT) and not suitable for other treatment options, such as second-time HSCT. CD19+ malignancies include:
• Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (ALL):
• Refractory ALL is defined as failure to achieve CR at the end of induction.
• Relapsed ALL is defined as reappearance of blasts in the blood or bone marrow (≥ 5%) or in any extramedullary site after a CR.
• Relapsed/Refractory B-cell originated Non-Hodgkin Lymphoma (NHL) including 1) de-novo diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, 2) large-B cell lymphoma transformed from indolent lymphomas, 3) follicular lymphoma of all grades, 4) mantle cell lymphoma, and 5) CD20(+) high-grade B-cell lymphomas. Refractory disease for lymphoma is defined as:
• Progressive disease or stable disease lasting \< 6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence \< 12 months after prior autologous HSCT.
• Prior therapy must have included an anti-CD20 monoclonal antibody-containing regimen and an anthracycline-containing chemotherapy regimen
• For patients with transformed follicular lymphoma (TFL), prior chemotherapy for follicular lymphoma and subsequent refractory disease after transformation to DLBCL.
• At least one measurable lesion, demonstrating that the nodal lesion is ≥ 1.5 cm in the longest diameter or the extranodal lesion is ≥ 1.0 cm in the longest diameter, according to the Lugano Classification (2014).
• Patients must have received at least 2 prior lines of therapy. HSCT (allogeneic or autologous) can be accounted as one of the prior line therapy, and the subjects must have been at least 3 months from prior HSCT.
• Karnofsky Performance Scale ≥ 60
• Patient able to provide written informed consent for participating in the study
• Age ≥ 20 years and ≤ 75 years old at the time of providing informed consent
• Patients shall be at least 3 weeks from the last cytotoxic chemotherapy before apheresis. Short-acting targeted therapies (e.g., tyrosine kinase inhibitors) must be stopped \> 72 hours before apheresis.

You may not qualify if:

• A subject who met any of the following criteria is not eligible to enter the study:
• Received previous treatment with anti-CD19 therapy;
• Is with a history of CNS malignancy and/or active CNS diseases;
• Has previous or concurrent malignancies other than CD19+ malignancies;
• Has active neurological, autoimmune, or inflammatory disorders;
• Has clinically significant cardiac diseases, or cardiac arrhythmia not controlled with medical treatment;
• Has cardiac involvement with lymphoma;
• Has any active infections, conditions, and diseases that may interfere with the assessment of safety and efficacy of the study deemed by the investigator or designee;
• Received live vaccine within 6 weeks of the screening
• Received radiation therapy within 2 weeks of the planned CAR-T cells infusion;
• Is with positive serology for HIV;
• Is with positive hepatitis B or hepatitis C infection, defined as positive HBs Ag or positive Anti-HCV Ab;
• Active graft versus host disease (GVHD) ≥ grade 2 using the CIBMTR Acute GVHD Grading System or requiring systemic steroid therapy greater than physiologic dosing; Note: Overall grading of GVHD is based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8, see the GVHD Grading and Staging table at CIBMTR Forms Instruction Manual (Last updated: 2020/03/10), page 301-303 (Available at https://www.cibmtr.org/manuals/fim, accessed on 08 Apr 2020).
• Use of investigational medicinal product within 30 days before the screening;
• Positive beta HCG in female of child-bearing potential (defined as not post-menopausal for 12 months) or history of previous surgical sterilization or lactating females.

Sponsors & Collaborators

• Eden BioCell Ltd.: lead
• National Taiwan University Hospital: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Non-Hodgkin; Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shangru Wu, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

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: 3+3 dose escalation

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 14, 2021
• Study Start: March 2, 2021
• Primary Completion: May 12, 2022
• Study Completion: May 12, 2022
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)