Active, not recruitingNCT03620058Updated Oct 14, 2025

CART22 Alone or in Combination With huCART19 for ALL

A Phase 1 interventional study of CART22-65s cells and huCART19 Cells in Chemotherapy Resistant Acute Lymphoblastic Leukemia and Refractory Acute Lymphoblastic Leukemia, sponsored by University of Pennsylvania. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-14.

Sponsored by University of Pennsylvania · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 23
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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 studied

Chemotherapy Resistant Acute Lymphoblastic Leukemia
Refractory Acute Lymphoblastic Leukemia

Browse trials for

Precursor Cell Lymphoblastic Leukemia-Lymphoma 2,061

In context

Precursor Cell Lymphoblastic Leukemia-Lymphoma

2,061 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 490 are open to participants now.

This study's enrollment of 23 is below the median of 40 across 1,653 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.

Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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:

CNS1 - no blasts seen on cytocentrifuge (CNS negative);
CNS2 - total nucleated cell count \<5x106/L, but blasts seen on cytocentrifuge;
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

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 23 participants (actual)

Study arms

Experimental
CART22-65s monotherapy
Biological: CART22-65s cells
Experimental
CART22-65s in combination with huCART19
Biological: CART22-65s cells · Biological: huCART19 Cells

Interventions

BiologicalCART22-65s cells
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
BiologicalhuCART19 Cells
Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB

What researchers measure

Primary outcomes

Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
Time frame: 15 months
Assess the safety of combination CART22-65s and huCART19 in relapsed/refractory ALL Subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
Time frame: 15 months

Secondary outcomes

Tumor response.
Overall Complete Remission Rate (ORR) at Day 28 which includes CR and CR with incomplete blood count recovery (CRi).
Time frame: 28 Days
Tumor response.
overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6
Time frame: 6 months
Tumor response.
overall survival (OS)
Time frame: 1 Year
Tumor response.
duration of remission (DOR)
Time frame: 1 Year
Tumor response.
relapse free survival (RFS)
Time frame: 1 Year
Tumor response.
event free survival (EFS)
Time frame: 1 Year
CAR T cell kinetics
Engraftment and persistence in blood by qPCR (or flow cytometry)
Time frame: 1 Year
CAR T cell kinetics
Trafficking to target tissue (bone marrow) or other tissues (cerebral spinal fluid and other tissues if available) as determined by qPCR (or flow cytometry).
Time frame: 1 Year
Evaluate bioactivity of CAR T cells
Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses
Time frame: 1 Year
Determine antigen expression and normal B cell levels in response to CAR T cells
Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry
Time frame: 1 Year

Study locations

1 site

University of Pennsylvania
Philadelphia, Pennsylvania 19104, United States

References and documents

Publications

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. PubMed 40246579 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 14, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03620058
Lead sponsor: University of Pennsylvania
Responsible party: Sponsor
First posted: Aug 8, 2018
Start date: Sep 27, 2018
Primary completion: Jan 2036 (estimated)
Completion: Jan 2036 (estimated)
Last update: Oct 14, 2025

Study contacts

Noelle Frey, MD

principal investigator · University of Pennsylvania

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.

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