Programmed Allogeneic CRISPR-edited T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (PACE CART19) in Patients With Relapsed Or Refractory CD19+ Leukemia and Lymphoma

NCT05037669 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: UPCC 27419
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase I trial to assess the safety and feasibility of administering pre-manufactured allogeneic T cells from healthy donors expressing CD19-targeting chimeric antigen receptors lacking expression of HLA class I, HLA class II molecules and endogenous TCR through CRISPR-mediated genome-editing of beta-2 microglobulin, CIITA and T cell receptor alpha chain, respectively. These cells are called PACE CART19 cells.

Conditions

Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Frequency and severity of adverse events

  28 days

• Time from consent to first PACE CART19 infusion.

  12 months

• The number of subjects consented and treated and the number of subjects consented but never treated will be described.

  12 months

Secondary Outcomes (10)

• Overall Response Rate (ORR)

  12 months

• Best Overall Response (BOR)

  12 months

• Overall Survival (OS)

  12 months

• Event-free survival (EFS)

  12 Months

• Duration of Response (DOR)

  12 Months

Study Arms (2)

Cohort A: Acute Lymphoblastic Leukemia (ALL)

EXPERIMENTAL

Adult patients aged \>18 with relapsed or refractory B cell malignancies - Acute Lymphoblastic Leukemia (ALL)

Biological: PACE CART19

Cohort B: Chronic Lymphocytic Leukemia (CLL) + Non-Hodgkin's Lymphoma (NHL)

EXPERIMENTAL

Adult patients aged \>18 with relapsed or refractory B cell malignancies - Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL).

Biological: PACE CART19

Interventions

PACE CART19 BIOLOGICAL

PACE CART19 cells are allogeneic T cells transduced with a lentiviral vector to express an anti-CD19 scFv TCRz:41BB and electroporated to temporarily express the CRISPR/Cas9 RNA system resulting in beta-2 microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA) and TCR-α chain (TRAC) targeted disruption. PACE CART19 cells will be administered by IV infusion.

Cohort A: Acute Lymphoblastic Leukemia (ALL); Cohort B: Chronic Lymphocytic Leukemia (CLL) + Non-Hodgkin's Lymphoma (NHL)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Documentation of CD19 expression on malignant cells
• a. ALL/CLL: At time of most recent relapse b. NHL: Within 6 months of physician-investigator confirmation of eligibility as long as there has been no intervening CD19 directed therapy since expression confirmed. Results outside of this window may be used, if there is no accessible tumor site and the subject did not receive intervening CD19 directed therapy since CD19 expression was confirmed.
• Patients with relapsed disease after prior autologous or allogeneic SCT must meet the following criteria:
• a. Have no active GVHD and require no immunosuppression b. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
• Adequate organ function defined as:
• Creatinine ≤ 1.6 mg/dl
• ALT/AST ≤ 3x upper limit of normal range
• Direct bilirubin ≤2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl)
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen \> 92% on room air, and DLCO ≥ 40% (corrected for anemia)
• Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
• Evidence of active disease. This could include circulating disease in the blood, disease in the bone marrow by standard morphology (or by MRD testing for ALL patients), or measurable disease per Lugano Criteria (NHL patients).
• Male or female age ≥ 18 years.
• ECOG Performance Status that is either 0 or 1.
• Subjects of reproductive potential must agree to use acceptable birth control methods.

You may not qualify if:

• Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
• Receipt of immune checkpoint inhibitors within 4 months prior to physician-investigator confirmation of eligibility.
• CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions.
• Pregnant or nursing (lactating) women.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Sponsors & Collaborators

• University of Pennsylvania: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Study Officials

• Noelle Frey, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: September 8, 2021
• Study Start: July 1, 2022
• Primary Completion: January 1, 2025
• Study Completion (Estimated): January 1, 2038
• Last Updated: June 22, 2023

Record last verified: 2022-03