Clinical Trials /

Phase 2 Trial of CD19 Redirected Autologous T Cells

NCT04276870

Description:

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).

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Trial of CD19 Redirected Autologous T Cells
  • Official Title: Phase 2 Trial of CD19-Directed Chimeric Antigen Receptor CD19 Redirected Autologous T Cells (CART19) for Orphan Indications of Pediatric B Cell Acute Lymphoblastic Leukemia (B ALL)

Clinical Trial IDs

  • ORG STUDY ID: 834653, 19CT023, 19-016979
  • NCT ID: NCT04276870

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

Interventions

DrugSynonymsArms
Murine CART19Infant subjects with very high risk KMT2A B-ALL

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Subjects with hypodiploid B-ALLExperimental
  • Murine CART19
Subjects with t(17;19) B-ALLExperimental
  • Murine CART19
Infant subjects with very high risk KMT2A B-ALLExperimental
  • Murine CART19
Subjects with central nervous system (CNS) relapse who did notExperimental
  • Murine CART19

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. Expression of CD19 on leukemic blasts demonstrated by flow cytometry of bone marrow,
             cerebrospinal fluid, or peripheral blood

          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.
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-free survival (EFS)
Time Frame:One year
Safety Issue:
Description:1 year event-free survival (EFS), where events include no response, relapse, death due to any cause

Secondary Outcome Measures

Measure:EFS Rate 1
Time Frame:One year
Safety Issue:
Description: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
Measure:To further evaluate the safety of CART19 in the target patient populations
Time Frame:One year
Safety Issue:
Description:Frequency and severity of adverse events
Measure:EFS rate 2
Time Frame:One year
Safety Issue:
Description: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
Measure:MRD conversion
Time Frame:One year
Safety Issue:
Description: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
Measure:Relapse Free survival 1
Time Frame:One year
Safety Issue:
Description: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.
Measure:Relapse Free survival 2
Time Frame:One year
Safety Issue:
Description: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
Measure:Relapse Free survival 3
Time Frame:One year
Safety Issue:
Description: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
Measure:Relapse Free survival 4
Time Frame:One year
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

February 17, 2020