Acute Lymphoblastic LeukemiaPhase 2NCT03792633
Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL
A Phase 2 study testing huCART19 in people with Acute Lymphoblastic Leukemia, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 3 months to 29 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- huCART19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2019to 4 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 3 months to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed informed consent form must be obtained.
- Relapsed or refractory B-cell ALL:
- Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who meet one of the following criteria:
- Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (>25% blasts) at end of induction OR
- First marrow relapse of B-ALL at < 36 months from diagnosis OR iii. 2nd or greater relapse OR
- Any relapse after allogeneic HSCT and ≥ 4 months from SCT at enrollment OR
Show all 21Show fewer
- Refractory disease defined as having not achieved an MRD-negative and/or CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of reinduction therapy for patients in first relapse OR
- Ineligible for allogeneic SCT because of:
- Comorbid disease
- Other contraindications to allogeneic SCT conditioning regimen
- Lack of suitable donor
- Prior SCT
- Declines allogeneic SCT as the therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a BMT physician not part of the study team b. Cohort B: Patients previously treated with B cell directed engineered cell therapy who meet one of the following criteria: i. partial response or no response to prior cell therapy ii. CD19+ relapse after prior cell therapy iii. demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of engineered cells c. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.3 of the protocol)
- 3. Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue by flow cytometry at relapse (or a recent sample in the case of refractory disease). If the patient has received CD19-directed therapy, then the flow cytometry should be obtained after this therapy to show CD19 expression.
- 4. Adequate organ function defined as:
- A serum creatinine based on age/gender
- ALT≤ 500 U/L
- Bilirubin ≤2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
- Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist.
- 5. Age 3 months to 29 years. 6. Adequate performance status (Lansky or Karnofsky score ≥50). 7. 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-versus-host disease (GVHD) 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.
- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- Pregnant or nursing (lactating) women.
- Uncontrolled active infection.
- Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS or neurotoxicity.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)
This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 3 months - 29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- huCART19
- 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.
huCART19Biological
IV injection
| Study group | Role | What they receive |
|---|---|---|
| Newly Diagnosed VHR B-ALL or High-Risk Relapse of B | Experimental | Not described Receives: Biological: huCART19 |
| Poor Response to Prior B Cell Directed Engineered cell therapy | Experimental | Not described Receives: Biological: huCART19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment.
Time from infusion to the first of event or censoring Events = Relapse, No Response, or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Measured: 1 year
Number of Subjects With Event-Free Survival in Patients With Poor Response to Prior B Cell Directed Engineered Cell Therapy 1 Year After Treatment.
Time from infusion to the first of event or censoring Events = Relapse, No Response (including CR/CRi without B Cell Aplasia), or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Measured: 1 year
Secondary outcomes (3)
Overall Remission Rate
Overall remission rate as determined by the response at day 28, computed as the number of subjects with CR or Cri, in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL.
Measured: 28 Days
Overall Remission Rate (Cohort B)
Number of subjects with CR/CRi with B Cell Aplasia at Day 28
Measured: 28 Days
Percentage of Subjects With Relapse-free Survival
Time from first response of CR/CRi to the first of event or censoring, in responders.
Cohort A: Events = Relapse or Death; Censoring = Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Cohort B: When defining responders, CR/CRi without B Cell Aplasia is considered no response. Events = Relapse or Death; Censoring = Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
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 posted3 Jan 2019
- Study start18 Jan 2019
- Primary completion4 Apr 2024
- Study completion4 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Sponsor
- Investigators
- Shannon Maude, MD, PhD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03792633
- Sponsor's protocol ID
- 831916
- Other IDs
- 18CT014
- Status last verified
- May 2025
- First submitted
- 2 Jan 2019
- Last updated
- 5 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)
- ClinicalTrials.gov ID
- NCT03792633
- Acronym / sponsor ID
- 831916
- Conditions
- Acute Lymphoblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Study start
- 18 Jan 2019 (actual)
- Primary completion
- 4 Apr 2024 (actual)
- Study completion
- 4 Apr 2024 (actual)
- First posted
- 3 Jan 2019 (actual)
- Results
- Posted 16 May 2025
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 phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 3 months - 29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Newly Diagnosed VHR B-ALL or High-Risk Relapse of B | Experimental | Biological: huCART19 |
| Poor Response to Prior B Cell Directed Engineered cell therapy | Experimental | Biological: huCART19 |
Who may qualify
- Ages
- 3 months to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Signed informed consent form must be obtained.
- Relapsed or refractory B-cell ALL:
- First marrow relapse of B-ALL at < 36 months from diagnosis OR iii. 2nd or greater relapse OR
- Any relapse after allogeneic HSCT and ≥ 4 months from SCT at enrollment OR
- Refractory disease defined as having not achieved an MRD-negative and/or CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of reinduction therapy for patients in first relapse OR
Key exclusion criteria (8 listed)
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 |
|---|---|---|
| huCART19IV injection | Biological | Newly Diagnosed VHR B-ALL or High-Risk Relapse of B, Poor Response to Prior B Cell Directed Engineered cell therapy |
Primary outcome
Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment.
Time frame: 1 year
Time from infusion to the first of event or censoring Events = Relapse, No Response, or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Number of Subjects With Event-Free Survival in Patients With Poor Response to Prior B Cell Directed Engineered Cell Therapy 1 Year After Treatment.
Time frame: 1 year
Time from infusion to the first of event or censoring Events = Relapse, No Response (including CR/CRi without B Cell Aplasia), or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
3 secondary outcomes
Overall Remission Rate
Time frame: 28 Days
Overall Remission Rate (Cohort B)
Time frame: 28 Days
Percentage of Subjects With Relapse-free Survival
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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. This study is not recruiting at the moment.
Shannon Maude, MD, PhD 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 2 study testing huCART19 in people with 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 21 inclusion and 8 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: finished, as of the sponsor's last update on 5 Jun 2025. 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 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?
Yes. Results are posted in the registry (first posted 16 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment. (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 5 Jun 2025.