CART22 Alone or in Combination With huCART19 for ALL

NCT ID: NCT03620058

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-27
• Study Completion Date: 2036-01-31

Brief Summary

This is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.

Conditions

Chemotherapy Resistant Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CART22-65s monotherapy

Group Type: EXPERIMENTAL

CART22-65s cells

Intervention Type: BIOLOGICAL

Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB

CART22-65s in combination with huCART19

Group Type: EXPERIMENTAL

CART22-65s cells

Intervention Type: BIOLOGICAL

Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB

huCART19 Cells

Intervention Type: BIOLOGICAL

Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB

Interventions

CART22-65s cells

Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB

Intervention Type: BIOLOGICAL

huCART19 Cells

Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 1. Patients with relapsed or refractory B cell ALL:

a. Patients with 2nd or greater relapse or refractory to 1st salvage as defined by: i. Recurrent disease in the bone marrow identified morphologically, by immunohistochemistry or by Flow cytometry.

ii. Patients with extramedullary relapse only (no bone marrow involvement) will be eligible if disease response can be assessed radiographically b. Patients with refractory disease as defined by: i. Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of induction chemotherapy ii. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.

c. Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.

d. Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.

i. *CNS disease definitions:

1. CNS1 - no blasts seen on cytocentrifuge (CNS negative);

2. CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;

3. CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve palsy).

• 2. For Cohort 1: Documentation of CD22 expression on malignant cells at relapse. For Cohort 2: Documentation of CD22 and/or CD19
• 3. Adequate vital organ function defined as:

1. Creatinine ≤ 1.6 mg/dl

2. ALT/AST ≤ 3x upper limit of normal range

3. Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct bilirubin does not need to be assessed.

4. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA

• 4. Male or female age ≥ 18 years.
• 5. ECOG Performance Status that is either 0 or 1.
• 6. No contraindications for leukapheresis.
• 7. Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria

• 1. Active hepatitis B or active hepatitis C.
• 2. HIV Infection.
• 3. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• 4. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of eligibility confirmation by physician-investigator.
• 5. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
• 6. Planned concurrent treatment with systemic steroids or immunosuppressant medications. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions or adrenal insufficiency. For additional details regarding use of steroid and immunosuppressant medications.
• 7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• 8. Pregnant or nursing (lactating) women.
• 10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noelle Frey, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Myers RM, DiNofia AM, Li Y, Diorio C, Liu H, Wertheim G, Fraietta JA, Gonzalez V, Plesa G, Siegel DL, Iannone E, Shinehouse L, Brogdon JL, Taylor C, Jadlowsky JK, Hexner EO, Engels B, Baniewicz D, Callahan C, Ruella M, Aplenc R, Barz Leahy A, McClory SE, Rheingold SR, Wray L, June CH, Maude SL, Frey NV, Grupp SA. CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy. J Immunother Cancer. 2025 Apr 17;13(4):e011549. doi: 10.1136/jitc-2025-011549.

Reference Type: DERIVED

PMID: 40246579 (View on PubMed)

Other Identifiers

IRB # 830049; UPCC #12418

Identifier Type: -

Identifier Source: org_study_id