B-cell Acute Lymphoblastic LeukemiaPhase 1/2NCT05674175
Co-administration of CART22-65s and huCART19 for B-ALL
A Phase 1/2 study testing Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s) and Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) in people with B-cell Acute Lymphoblastic Leukemia and B Lineage Lymphoblastic Lymphoma, run by Stephan Grupp MD PhD at 1 site in United States.
Trial summary
This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL). Read more about this study
- Who is it for?
- Ages Up to 29 years
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia, B Lineage Lymphoblastic Lymphoma
- What is being tested?
- Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s) and Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2023to 1 Jul 2029
- Phase
- Phase 1/2
- 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 Up to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed informed consent form
- Patients with documented CD19+ and/or CD22+ ALL/LLy:
- Cohort A: Patients with relapsed or refractory ALL/LLy:
- Cohort B: Patients with poor response to prior B cell directed engineered cell therapy
- Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy
- Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression.
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- Age 0-29 years
- Adequate organ function
- Adequate performance status defined as Lanksy or Karnofsky performance score ≥50.
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- Active hepatitis B or active hepatitis C
- HIV infection
- Active acute or chronic Graft Vs. Host Disease requiring systemic therapy
- Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- Central nervous system disease that is progressive on therapy, or with Central nervous system parenchymal lesions that might increase the risk of central nervous system toxicity.
- Pregnant or nursing (lactating) women
- Uncontrolled active infection
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
CART Nurse Navigator, 445-942-5891, cartnursenavigator@chop.edu
Melissa Varghese, M.S., 8455535358, varghesem@chop.edu
About this study
Official title: Use of Autologous Anti-CD22 CAR T Cells (CART22-65s) Co-administered With Humanized Anti-CD19 CAR T Cells (huCART19) in Children and Young Adults With Relapsed or Refractory B-ALL
This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).
Read the detailed description
CD19-targeted CAR T cell therapy has transformed the treatment landscape for children and young adults with chemo-refractory or relapsed B cell Acute Lymphoblastic Leukemia (B-ALL). Despite remarkable initial response rates, approximately 50% of pediatric patients experience a subsequent disease relapse. The prognosis for these patients is dismal with a median survival of less than one year from the time of post-CART19 relapse. The primary mechanisms contributing to CART19 failure include CD19-antigen escape and loss of CAR T cell surveillance due to short CART persistence. This study aims to counter each driver of relapse by co-administering two next-generation CAR T cell products: an anti-CD22 CART (CART22-65s), designed to overcome CD19-antigen escape; and a humanized anti-CD19 CART (huCART19), designed to overcome immune-mediated rejection of murine CART19.
- Being tested
- Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s), Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)
- Medical subject headings
- Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)Biological
Also called CART22-65s
CART22-65s are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD22 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain
Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)Biological
Also called huCART19
HuCART19 cells are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD19 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain
| Study group | Role | What they receive |
|---|---|---|
| Dose Finding Arm | Experimental | Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities Receives: Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s); Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) |
| Expansion Arm | Experimental | If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) \& Cohort B (prior treatment with a prior CAR T cell product). Receives: Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s); Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of CART22-65s and huCART19 co-administration
The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory B-Cell Acute Lymphoblastic Leukemia or B Cell Lymphoblastic Lymphoma (B-LLy), including those previously treated with cell therapy.
Measured: 1 year
Efficacy of CART22-65s and huCART19 co-administration
The efficacy of CART22-65s and huCART19 co-administration will be measured by the evaluating the overall response rate in patients with advanced or refractory B cell hematologic malignancies, including those previously treated with cell therapy.
Measured: 1 year
Secondary outcomes (7)
Manufacturing Feasibility
The manufacturing feasibility of manufacturing both CART22-65s and huCART19 will be measured by the percentage of manufactured products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.
Measured: 5 years
Anti-tumor response due to CART22-65s and huCART19 co-administration
Anti-tumor response due to CART22-65s and huCART19 co-administration will be measured by negative minimal residual disease (MRD) as measured by multiparameter flow cytometry at day 28.
Measured: Day 28
Event Free Survival
1-year Event-Free Survival (EFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B)
Measured: 1 year
Relapse Free Survival
1-year relapse-free survival (RFS) rate in CAR-naïve subjects with relapsed/refractory B-ALL (Cohort A) and in CAR-exposed subjects with poor response to prior B cell directed engineered cell therapy (Cohort B)
Measured: 1 year
Overall Survival
1-year overall survival (OS) rate in CAR-naïve subjects with relapsed/refractory B-ALL (Cohort A) and in CAR-exposed subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Measured: 1 year
CAR T Cell Therapy Persistence
CART22-65s and huCART19 persistence polymerase chain reaction (or flow cytometry) analysis of whole blood to detect and quantify survival of CART2265s and huCART19 over time.
Measured: 1 year
Bioreactivity of CART22-65s and huCART19 when co-administered
The bioreactivity of CART22-65s and huCART19 when co-administered, as measured by elevations level in any of; Uric Acid, Lactate Dehydrogenase (LDH), c-reactive protein (CRP), and cytokines (e.g.IL -10) before and after CART T cell infusions.
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 posted6 Jan 2023
- Study start25 Jan 2023
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 93 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stephan Grupp MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania
- Responsible party
- Sponsor-investigator, Stephan Grupp MD PhD, Children's Hospital of Philadelphia
- Investigators
- Regina Myers, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05674175
- Sponsor's protocol ID
- 22-020640
- Other IDs
- 22CT015
- Status last verified
- Mar 2026
- First submitted
- 6 Dec 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Autologous Anti-CD22 CAR T Cells (CART22-65s) Co-administered With Humanized Anti-CD19 CAR T Cells (huCART19) in Children and Young Adults With Relapsed or Refractory B-ALL
- ClinicalTrials.gov ID
- NCT05674175
- Acronym / sponsor ID
- 22-020640
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 93 participants (estimated)
- Lead sponsor
- Stephan Grupp MD PhDUniversity, hospital or other
- Collaborators
- University of Pennsylvania
- Study start
- 25 Jan 2023 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 6 Jan 2023 (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 study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).
Detailed description
CD19-targeted CAR T cell therapy has transformed the treatment landscape for children and young adults with chemo-refractory or relapsed B cell Acute Lymphoblastic Leukemia (B-ALL). Despite remarkable initial response rates, approximately 50% of pediatric patients experience a subsequent disease relapse. The prognosis for these patients is dismal with a median survival of less than one year from the time of post-CART19 relapse. The primary mechanisms contributing to CART19 failure include CD19-antigen escape and loss of CAR T cell surveillance due to short CART persistence. This study aims to counter each driver of relapse by co-administering two next-generation CAR T cell products: an anti-CD22 CART (CART22-65s), designed to overcome CD19-antigen escape; and a humanized anti-CD19 CART (huCART19), designed to overcome immune-mediated rejection of murine CART19.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Finding Arm | Experimental | Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s), Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities |
| Expansion Arm | Experimental | Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s), Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) \& Cohort B (prior treatment with a prior CAR T cell product). |
Who may qualify
- Ages
- Up to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Signed informed consent form
- Patients with documented CD19+ and/or CD22+ ALL/LLy:
- Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy
- Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression.
- Age 0-29 years
Key exclusion criteria (7 listed)
- Active hepatitis B or active hepatitis C
- HIV infection
- Active acute or chronic Graft Vs. Host Disease requiring systemic therapy
- Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- Central nervous system disease that is progressive on therapy, or with Central nervous system parenchymal lesions that might increase the risk of central nervous system toxicity.
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 |
|---|---|---|
| Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)Also: CART22-65sCART22-65s are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD22 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain | Biological | Dose Finding Arm, Expansion Arm |
| Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)Also: huCART19HuCART19 cells are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD19 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain | Biological | Dose Finding Arm, Expansion Arm |
Primary outcome
Safety of CART22-65s and huCART19 co-administration
Time frame: 1 year
The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory B-Cell Acute Lymphoblastic Leukemia or B Cell Lymphoblastic Lymphoma (B-LLy), including those previously treated with cell therapy.
Efficacy of CART22-65s and huCART19 co-administration
Time frame: 1 year
The efficacy of CART22-65s and huCART19 co-administration will be measured by the evaluating the overall response rate in patients with advanced or refractory B cell hematologic malignancies, including those previously treated with cell therapy.
7 secondary outcomes
Manufacturing Feasibility
Time frame: 5 years
Anti-tumor response due to CART22-65s and huCART19 co-administration
Time frame: Day 28
Event Free Survival
Time frame: 1 year
Relapse Free Survival
Time frame: 1 year
Overall Survival
Time frame: 1 year
CAR T Cell Therapy Persistence
Time frame: 1 year
Bioreactivity of CART22-65s and huCART19 when co-administered
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 27 Mar 2026.
- Individual participant dataSharing planned: No
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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.
Regina Myers, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s) and Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) in people with B-cell Acute Lymphoblastic Leukemia and B Lineage Lymphoblastic Lymphoma, run by Stephan Grupp MD PhD 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 10 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 27 Mar 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact CART Nurse Navigator (445-942-5891, CARTNurseNavigator@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of CART22-65s and huCART19 co-administration (time frame: 1 year). 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?
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 27 Mar 2026.