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Acute Lymphoblastic LeukemiaPhase 1NCT05037669

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

A Phase 1 study testing PACE CART19 in people with Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia, run by University of Pennsylvania.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PACE CART19
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jul 2022to Jan 2038
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent form
  • Documentation of CD19 expression on malignant cells
  • 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:
  • 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:
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  • 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.
  • Disease-specific criteria:
  • Cohort A i. Patients with relapsed or refractory B cell ALL which meets one of the following criteria:
  • <!-- -->
  • Relapsed or refractory B cell ALL with 2nd or greater relapse or refractory to 1st salvage as defined by:
  • Recurrent disease in the blood or bone marrow identified morphologically, by immunohistochemistry or by Flow cytometry.
  • Patients with extramedullary relapse only (no bone marrow involvement) will be eligible if disease response can be assessed radiographically, OR
  • Refractory B cell ALL as defined by:
  • Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of induction chemotherapy b. Patients that achieve morphologic remission but remain MRD+ after ≥2 cycles of induction chemotherapy, OR
  • Ph+ relapsed or refractory B cell ALL that is intolerant to or have failed a tyrosine kinase inhibitor therapy containing regimen.
  • Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.2) 1. *CNS disease definitions70:
  • CNS1 - no blasts seen on cytocentrifuge (CNS negative); b. CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge; c. CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve palsy).
  • Cohort B (CLL) i. Patients must have relapsed/refractory disease after at least 2 prior lines of appropriate therapy, AND ii. Patients must have previously received, or be intolerant to an approved BTK inhibitor and venetoclax; unless a BTK inhibitor or venetoclax is contraindicated.
  • Cohort B (NHL)- With one of the following diagnoses: i. Diffuse Large B-cell Lymphoma
  • Patients with any of the following histologies:
  • Diffuse large B-cell lymphoma (DLBCL), NOS
  • Germinal center B-cell type ii. Activated B-cell type b. Primary cutaneous DLBCL, leg type c. Primary mediastinal (thymic) large B-cell lymphoma d. ALK+ large B-cell lymphoma e. High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (i.e. "Double or Triple Hit") f. High-grade B-cell lymphoma, NOS
  • Patients must have relapsed after, or be ineligible for, prior CAR T cell therapy, and meet one of the following criteria:
  • Relapsed/refractory disease after at least 2 prior lines of appropriate therapy and are ineligible for autologous stem cell transplant or commercial CAR T cell therapy.
  • Relapse/refractory disease after autologous SCT.
  • Relapsed/refractory disease after allogeneic SCT. ii. Large cell transformation of CLL (Richter's transformation)
  • 1. Patients must be primary refractory or received at least 1 prior line of treatment.
  • Follicular lymphoma 1. Patients who have received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy), AND 2. Progressed within 2 years after second or higher line of therapy. iv. Mantle cell lymphoma
  • Patients must have either failed or be ineligible for standard of care Tecartus™ (brexucabtagene autoleucel) or other investigational CAR T cell product; and
  • Patients must also meet one of the following criteria:
  • Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
  • Relapsed/refractory disease after prior autologous SCT.
  • Relapsed/refractory disease after prior allogeneic SCT..

Who cannot join

  • 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.
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  • 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.

About this study

Official title: Phase I Trial of Programmed Allogeneic CRISPR-edited T Cells (PACE) Gene Edited to Eliminate Endogenous TCR, HLA-class I and HLA-class II and Engineered to Express Anti-CD19 Chimeric Antigen Receptor (PACE CART19) in Patients With Relapsed Or Refractory CD19+ Leukemia and Lymphoma

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.

Being tested
PACE CART19
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PACE CART19Biological

    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.

Study groups in NCT05037669
Study groupRoleWhat they receive
Cohort A: Acute Lymphoblastic Leukemia (ALL)ExperimentalAdult patients aged >18 with relapsed or refractory B cell malignancies - Acute Lymphoblastic Leukemia (ALL)
Receives: Biological: PACE CART19
Cohort B: Chronic Lymphocytic Leukemia (CLL) + Non-Hodgkin's Lymphoma (NHL)ExperimentalAdult patients aged >18 with relapsed or refractory B cell malignancies - Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL).
Receives: Biological: PACE CART19

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and severity of adverse events

    Measured: 28 days

  2. Time from consent to first PACE CART19 infusion.

    Measured: 12 months

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

    Measured: 12 months

Secondary outcomes (10)

  1. Overall Response Rate (ORR)

    Measured: 12 months

  2. Best Overall Response (BOR)

    Measured: 12 months

  3. Overall Survival (OS)

    Measured: 12 months

  4. Event-free survival (EFS)

    Measured: 12 Months

  5. Duration of Response (DOR)

    Measured: 12 Months

  6. Kinetics of expansion, persistence and homing to marrow and other organs of infused cells by quantitative PCR.

    Measured: 12 Months

  7. Kinetics of expansion, persistence and homing to marrow and other organs of infused cells by flow cytometry.

    Measured: 12 Months

  8. Systemic soluble immune factors in serum before and after treatment, and during CRS.

    Measured: 12 Months

  9. Polychromatic flow cytometry-based assessment of leukemia and B cells, extent and duration of leukemic response

    Measured: 12 Months

  10. Use of Next-Generation Immunoglobulin heavy chain Sequencing (NGIS) to quantitate presence or absence of malignant B cells

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2021
  2. Study startJul 2022 (estimated)
  3. Primary completionJan 2025 (estimated)
  4. Study completionJan 2038 (estimated)

Why it stopped: No available investigational product

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05037669
Sponsor's protocol ID
UPCC 27419
Status last verified
Mar 2022
First submitted
24 Aug 2021
Last updated
22 Jun 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PACE CART19 in people with Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia, run by University of Pennsylvania.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and severity of adverse events (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05037669.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.

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