Chemotherapy Resistant Acute Lymphoblastic LeukemiaPhase 1NCT03620058
CART22 Alone or in Combination With huCART19 for ALL
A Phase 1 study testing CART22-65s cells and huCART19 Cells in people with Chemotherapy Resistant Acute Lymphoblastic Leukemia and Refractory Acute Lymphoblastic Leukemia, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemotherapy Resistant Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- What is being tested?
- CART22-65s cells and huCART19 Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2018to Jan 2036
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 1. Patients with relapsed or refractory B cell ALL:
- 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.
- 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.
- Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.
- Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.
- *CNS disease definitions:
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- 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:
- Creatinine ≤ 1.6 mg/dl
- ALT/AST ≤ 3x upper limit of normal range
- Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct bilirubin does not need to be assessed.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1 Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells (CART22-65s) Alone and When Co-administered With Humanized Anti-CD19 Chimeric Antigen Receptor Redirected T Cells (huCART19) In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
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
- Being tested
- CART22-65s cells, huCART19 Cells
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART22-65s cellsBiological
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
huCART19 CellsBiological
Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB
| Study group | Role | What they receive |
|---|---|---|
| CART22-65s monotherapy | Experimental | Not described Receives: Biological: CART22-65s cells |
| CART22-65s in combination with huCART19 | Experimental | Not described Receives: Biological: CART22-65s cells; Biological: huCART19 Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 15 months
Secondary outcomes (10)
Tumor response.
Overall Complete Remission Rate (ORR) at Day 28 which includes CR and CR with incomplete blood count recovery (CRi).
Measured: 28 Days
Tumor response.
overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6
Measured: 6 months
Tumor response.
overall survival (OS)
Measured: 1 Year
Tumor response.
duration of remission (DOR)
Measured: 1 Year
Tumor response.
relapse free survival (RFS)
Measured: 1 Year
Tumor response.
event free survival (EFS)
Measured: 1 Year
CAR T cell kinetics
Engraftment and persistence in blood by qPCR (or flow cytometry)
Measured: 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).
Measured: 1 Year
Evaluate bioactivity of CAR T cells
Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses
Measured: 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
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start27 Sep 2018
- Primary completionJan 2036 (estimated)
- Study completionJan 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy Resistant Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noelle Frey, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03620058
- Sponsor's protocol ID
- IRB # 830049; UPCC #12418
- Status last verified
- Oct 2026
- First submitted
- 25 Jun 2018
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells (CART22-65s) Alone and When Co-administered With Humanized Anti-CD19 Chimeric Antigen Receptor Redirected T Cells (huCART19) In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT03620058
- Acronym / sponsor ID
- IRB # 830049; UPCC #12418
- Conditions
- Chemotherapy Resistant Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- Jan 2036 (estimated)
- Study completion
- Jan 2036 (estimated)
- First posted
- 8 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CART22-65s monotherapy | Experimental | Biological: CART22-65s cells |
| CART22-65s in combination with huCART19 | Experimental | Biological: CART22-65s cells, Biological: huCART19 Cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 1. Patients with relapsed or refractory B cell ALL:
- 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.
- 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.
- Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.
- Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CART22-65s cellsAutologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB | Biological | CART22-65s in combination with huCART19, CART22-65s monotherapy |
| huCART19 CellsAutologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB | Biological | CART22-65s in combination with huCART19 |
Primary outcome
Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
Time frame: 15 months
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
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.
Time frame: 15 months
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
10 secondary outcomes
Tumor response.
Time frame: 28 Days
Tumor response.
Time frame: 6 months
Tumor response.
Time frame: 1 Year
Tumor response.
Time frame: 1 Year
Tumor response.
Time frame: 1 Year
Tumor response.
Time frame: 1 Year
CAR T cell kinetics
Time frame: 1 Year
CAR T cell kinetics
Time frame: 1 Year
Evaluate bioactivity of CAR T cells
Time frame: 1 Year
Determine antigen expression and normal B cell levels in response to CAR T cells
Time frame: 1 Year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Derived from this study: PubMed 40246579Myers 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.
Related trials for Chemotherapy Resistant Acute Lymphoblastic Leukemia
Active, not recruitingPhase 1
CD22 Redirected Autologous T Cells for ALL
B Cell Leukemias, B Cell Lymphomas
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noelle Frey, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CART22-65s cells and huCART19 Cells in people with Chemotherapy Resistant Acute Lymphoblastic Leukemia and Refractory Acute Lymphoblastic Leukemia, run by University of Pennsylvania at 1 site in United States.
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 19 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
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?
Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0. (time frame: 15 months). The study lists 2 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 NCT03620058, which also lists 1 linked publication.
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 28 Oct 2026.