Orphan Indications for CD19 Redirected Autologous T Cells

NCT04276870 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 834653, 19CT023, 19-016979
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

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

Infants With Very High Risk KMT2A B-ALL; Pediatric and Young Adult Patientswith Hypodiploid or t(17;19) B-ALL; Patients With Central Nervous System Relapse Who Did Not Receive Cranial Radiation or Bone Marrow Transplantation

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  1 year event-free survival (EFS), where events include no response, relapse, death due to any cause

  One year

Secondary Outcomes (8)

• EFS Rate 1

  One year

• To further evaluate the safety of CART19 in the target patient populations

  One year

• EFS rate 2

  One year

• MRD conversion

  One year

• Relapse Free survival 1

  One year

Study Arms (4)

Subjects with hypodiploid B-ALL

EXPERIMENTAL

Biological: Murine CART19

Subjects with t(17;19) B-ALL

EXPERIMENTAL

Biological: Murine CART19

Infant subjects with very high risk KMT2A B-ALL

EXPERIMENTAL

Biological: Murine CART19

Subjects with central nervous system (CNS) relapse

EXPERIMENTAL

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

Biological: Murine CART19

Interventions

Murine CART19 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; Subjects with central nervous system (CNS) relapse; Subjects with hypodiploid B-ALL; Subjects with t(17;19) B-ALL

Eligibility Criteria

• Age: 0 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stephan Grupp MD PhD: lead
• University of Pennsylvania: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Study Officials

• Stephan Grupp, MD, PhD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

• Amanda DiNofia, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CART Nurse Navigator

CONTACT

445-942-5891; CARTNurseNavigator@chop.edu

Melissa S Varghese, M.S.

CONTACT

845-553-5358; varghesem@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Cancer Immunotherapy Program

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 19, 2020
• Study Start: March 12, 2020
• Primary Completion (Estimated): March 10, 2028
• Study Completion (Estimated): March 10, 2037
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)