Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALLPhase 2NCT04276870
Orphan Indications for CD19 Redirected Autologous T Cells
A Phase 2 study testing Murine CART19 in people with Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALL and Infants With Very High Risk KMT2A B-ALL, run by Stephan Grupp MD PhD at 1 site in United States.
Trial summary
This is an open-label, four-cohort, phase 2 study to determine the efficacy of CART19 in pediatric and young adult patientswith hypodiploid (Cohort A) or t(17;19) B-ALL (Cohort B), infants with very high risk KMT2A B-ALL (Cohort C), and in patients with central nervous system (CNS) relapse who did not receive cranial… Read more about this study
- Who is it for?
- Ages 0 to 29 years
- Conditions the study is for
- Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALL, Infants With Very High Risk KMT2A B-ALL, Patients With Central Nervous System Relapse Who Did Not Receive Cranial Radiation or Bone Marrow Transplantation
- What is being tested?
- Murine CART19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2020to 10 Mar 2037
- Phase
- Phase 2
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 0 to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed informed consent form must be obtained prior to any study procedure.
- Male and female patients with documented CD19+ B-ALL
- a.Cohort A \& B: Patients, regardless their response to initial or relapsed B ALL therapy, with the following characteristics: i.Cohort A: Subjects with confirmation of a hypodiploid karyotype (chromosome number fewer than 45) ii.Cohort B: Subjects with cytogenetic confirmation of the chromosomal translocation t(17;19) (Cohort B) b.Cohort C: Infants w/ newly diagnosed KMT2A rearranged B-ALL classified as very high risk by the following criteria: i.Age < 3 months at diagnosis ii.Age < 6 months and WBC > 300,000x109/L at diagnosis or a poor prednisone response in induction iii.MRD positive > 0.01 (or PCR > 104) after 2 courses of standard infant ALL therapy.
- c.Cohort D: Subjects in a first or greater CNS relapse, prior to therapy with cranial XRT or HSCT for the current relapse
- Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue.
- Age 0 to 29 years
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- Adequate organ function defined as:
- A serum creatinine based on age/gender as follows:
- Maximum Serum Creatinine (mg/dL) Age Male Female 0 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1.0 1.0 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4
- Adequate liver function:
- i.ALT≤ 5 x ULN; ALT ii.Total bilirubin ≤ 3 x ULN iii.ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.
- c.Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the physician-investigator.
- d.Left Ventricular Shortening Fraction (LVSF) ≥ 28%, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% by echocardiogram. In cases where quanitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualititatively normal ventricular function wll suffice.
- Adequate performance status defined as Lansky or Karnofsky score ≥ 50
- Subjects of reproductive potential must agree to use acceptable birth control methods
Who cannot join
- For subjects with a CNS relapse, prior cranial XRT or BMT for the current relapse is an exclusion.
- 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 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 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.
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
Amanda DiNofia, MD, 2155905476, DiNofiaA@chop.edu
About this study
Official title: CD19-Directed Chimeric Antigen Receptor CD19 Redirected Autologous T Cells (CART19) for Orphan Indications of Pediatric B Cell Acute Lymphoblastic Leukemia (B ALL)
This is an open-label, four-cohort, phase 2 study to determine the efficacy of CART19 in pediatric and young adult patientswith hypodiploid (Cohort A) or t(17;19) B-ALL (Cohort B), infants with very high risk KMT2A B-ALL (Cohort C), and in patients with central nervous system (CNS) relapse who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT) (Cohort D).
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Murine CART19Biological
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection with a planned dose of 5x106 CART19 cells/kg on day 0 with possible reinfusion/retreatment
| Study group | Role | What they receive |
|---|---|---|
| Subjects with hypodiploid B-ALL | Experimental | Not described Receives: Biological: Murine CART19 |
| Subjects with t(17;19) B-ALL | Experimental | Not described Receives: Biological: Murine CART19 |
| Infant subjects with very high risk KMT2A B-ALL | Experimental | Not described Receives: Biological: Murine CART19 |
| Subjects with central nervous system (CNS) relapse | Experimental | who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT) Receives: Biological: Murine CART19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
1 year event-free survival (EFS), where events include no response, relapse, death due to any cause
Measured: One year
Secondary outcomes (8)
EFS Rate 1
Modified EFS rate in CNS relapse patients, using a definition of events that includes no response, relapse, death, need for XRT or need for BMT
Measured: One year
To further evaluate the safety of CART19 in the target patient populations
Frequency and severity of adverse events
Measured: One year
EFS rate 2
Modified EFS rate in patients with early CNS relapsed B-ALL (CR1 <18 months) and those with late CNS relapsed B-ALL (CR1 >18 months) using a definition of events that includes no response, relapse, death, need for XRT or need for BMT
Measured: One year
MRD conversion
Rate of MRD conversion to less than 0.01% (in patients with MRD) 28 days after CART19 therapy in patients with t(17;19) B-ALL, hypodiploid B-ALL, and very high risk infant B-ALL
Measured: One year
Relapse Free survival 1
Relapse-free survival (RFS) at one year in patients with hypodiploid B-ALL, patients with t(17;19) B-ALL, and very high risk infant B-ALL regardless of their initial response to B-ALL therapy and in patients with CNS relapse who did not receive cranial XRT or BMT after CART19 and who achieved a complete remission following CART19 therapy.
Measured: One year
Relapse Free survival 2
RFS at one year in patients with hypodiploid B-ALL who were MRD negative at end of induction and those who were MRD positive at end of induction during upfront therapy
Measured: One year
Relapse Free survival 3
RFS at one year in patients with t(17;19) B-ALL who were MRD negative at end of induction and those who were MRD positive at end of induction during upfront therapy
Measured: One year
Relapse Free survival 4
RFS at one year in very high risk infants with KMT2A rearrangement who were MRD negative at end of induction and those who were MRD positive at end of induction.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start12 Mar 2020
- Primary completion10 Mar 2028 (estimated)
- Study completion10 Mar 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALLStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 133 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
- Stephan Grupp, MD, PhD, Study director, Children's Hospital of PhiladelphiaAmanda DiNofia, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276870
- Sponsor's protocol ID
- 834653, 19CT023, 19-016979
- Status last verified
- Mar 2026
- First submitted
- 14 Feb 2020
- Last updated
- 6 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No