Clinical trial NCT04276870: Orphan Indications for CD19 Redirected Autologous T Cells
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
First posted: 2020-02-19
Enrollment: 133
Sex: ALL
Minimum age (years): 0
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: One year
Secondary outcomes:
measure: EFS Rate 1
timeFrame: One year
measure: To further evaluate the safety of CART19 in the target patient populations
timeFrame: One year
measure: EFS rate 2
timeFrame: One year
measure: MRD conversion
timeFrame: One year
measure: Relapse Free survival 1
timeFrame: One year
measure: Relapse Free survival 2
timeFrame: One year
measure: Relapse Free survival 3
timeFrame: One year
measure: Relapse Free survival 4
timeFrame: One year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Stephan Grupp, MD, PhD
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Philadelphia
name: Amanda DiNofia, MD
role: PRINCIPAL_INVESTIGATOR
References: