Orphan Indications for CD19 Redirected Autologous T Cells

NCT ID: NCT04276870

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-12
• Study Completion Date: 2037-03-10

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 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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subjects with hypodiploid B-ALL

Group Type: EXPERIMENTAL

Murine CART19

Intervention Type: BIOLOGICAL

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

Subjects with t(17;19) B-ALL

Group Type: EXPERIMENTAL

Murine CART19

Intervention Type: BIOLOGICAL

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

Infant subjects with very high risk KMT2A B-ALL

Group Type: EXPERIMENTAL

Murine CART19

Intervention Type: BIOLOGICAL

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

Subjects with central nervous system (CNS) relapse

who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT)

Group Type: EXPERIMENTAL

Murine CART19

Intervention Type: BIOLOGICAL

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

Interventions

Murine CART19

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent form must be obtained prior to any study procedure.

2. 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

3. Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue.

4. Age 0 to 29 years

5. Adequate organ function defined as:

1. 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

2. 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.

6. Adequate performance status defined as Lansky or Karnofsky score ≥ 50

7. Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

1. For subjects with a CNS relapse, prior cranial XRT or BMT for the current relapse is an exclusion.

2. Active hepatitis B or active hepatitis C.

3. HIV Infection.

4. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.

5. 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.

6. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.

7. Pregnant or nursing (lactating) women.

8. Uncontrolled active infection.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Stephan Grupp MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Stephan Grupp MD PhD

Director, Cancer Immunotherapy Program

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Stephan Grupp, MD, PhD

Role: STUDY_DIRECTOR

Children's Hospital of Philadelphia

Amanda DiNofia, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

CART Nurse Navigator

Role: CONTACT

CARTNurseNavigator@chop.edu

445-942-5891

Melissa S Varghese, M.S.

Role: CONTACT

varghesem@chop.edu

845-553-5358

Facility Contacts

Amanda DiNofia, MD

Role: primary

DiNofiaA@chop.edu

2155905476

Other Identifiers

834653, 19CT023, 19-016979

Identifier Type: -

Identifier Source: org_study_id