Clinical Trials /

Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL

NCT03792633

Description:

This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 1-29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL
  • Official Title: Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)

Clinical Trial IDs

  • ORG STUDY ID: 831916
  • SECONDARY ID: 18CT014
  • NCT ID: NCT03792633

Conditions

  • Acute Lymphoid Leukemia

Interventions

DrugSynonymsArms
huCART19huCTL019Newly Diagnosed VHR B-ALL or High-Risk Relapse of B

Purpose

This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 1-29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.

Trial Arms

NameTypeDescriptionInterventions
Newly Diagnosed VHR B-ALL or High-Risk Relapse of BExperimental
  • huCART19
Poor Response to Prior B Cell Directed Engineered cell therapyExperimental
  • huCART19

Eligibility Criteria

        Inclusion Criteria:

        Relapsed or refractory B-cell ALL:

          -  Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who
             meet one of the following criteria:

               -  Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (>25% blasts) at
                  end of induction OR

               -  First marrow relapse of B-ALL at < 36 months from diagnosis OR

               -  2nd or greater relapse OR

               -  Any relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and ≥
                  4 months from stem cell transplant (SCT) at enrollment OR

               -  Refractory disease defined as having not achieved a minimal residual disease
                  (MRD)_-negative and/or cerebral spinal fluid (CSF)-negative complete response
                  (CR) after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of
                  reinduction therapy for patients in first relapse OR

               -  Ineligible for allogeneic stem cell transplant

          -  Cohort B: Patients previously treated with B cell directed engineered cell therapy who
             meet one of the following criteria:

               -  partial response or no response to prior cell therapy

               -  CD19+ relapse after prior cell therapy

               -  demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of
                  engineered cells

          -  Patients with prior or current history of CNS3 disease will be eligible if central
             nervous system (CNS) disease is responsive to therapy

          -  Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor
             tissue by flow cytometry at relapse

          -  Adequate organ function

          -  Age 1-29 years

          -  Adequate performance status

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:1-year Event-Free Survival in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL
Time Frame:1 year
Safety Issue:
Description:

Details

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

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