Status:
RECRUITING
Orphan Indications for CD19 Redirected Autologous T Cells
Lead Sponsor:
Stephan Grupp MD PhD
Collaborating Sponsors:
University of Pennsylvania
Conditions:
Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALL
Infants With Very High Risk KMT2A B-ALL
Eligibility:
All Genders
Up to 29 years
Phase:
PHASE2
Brief 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 h...
Eligibility Criteria
Inclusion
- 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
- 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
Exclusion
- 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.
Key Trial Info
Start Date :
March 12 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 10 2037
Estimated Enrollment :
133 Patients enrolled
Trial Details
Trial ID
NCT04276870
Start Date
March 12 2020
End Date
March 10 2037
Last Update
October 21 2025
Active Locations (1)
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1
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104