Clinical Trials /

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL

NCT04544592

Description:

Pediatric patients with refractory or multiply relapsed leukemia and lymphoma do very poorly with traditional chemotherapy and have overall survival rates of well under 20%. There has been much excitement over the development of Car T cell therapy for these types of leukemia/lymphoma, but many patients may not fit the standard criteria to receive them or they cannot tolerate the extended wait and ongoing therapy that is needed for manufacture of these cells at the commercial level. With this study, the investigators will investigate a new CD19 directed CAR-T therapy that will be manufactured locally with a goal of wider patient inclusion and less delay to CAR-T infusion. The investigators hypothesize that CD19 directed CAR-T cells manufactured using the Prodigy ClinicMACS system developed by Miltenyi (UCD19 CAR-T) will be safe and tolerable and show preliminary efficacy in pediatric patients with relapsed and/or refractory B-ALL or B- NHL

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL
  • Official Title: Phase 1/2 Dose Escalation and Preliminary Efficacy of CD19 Directed Car T Cells Generated Using The Miltenyi Clinimacs Prodigy System (UCD19 CarT) in Pediatric Patients With Relapsed and/or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) and B-Cell Non-Hodgkins Lymphoma(B-NHL)

Clinical Trial IDs

  • ORG STUDY ID: 18-2424.cc
  • SECONDARY ID: P30CA046934
  • NCT ID: NCT04544592

Conditions

  • B-cell Acute Lymphoblastic Leukemia
  • B-cell Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CD19CAR-CD3Zeta-4-1BB-Expressing Allogeneic T-Lymphocyte CellsUCD19 CART infusion

Purpose

Pediatric patients with refractory or multiply relapsed leukemia and lymphoma do very poorly with traditional chemotherapy and have overall survival rates of well under 20%. There has been much excitement over the development of Car T cell therapy for these types of leukemia/lymphoma, but many patients may not fit the standard criteria to receive them or they cannot tolerate the extended wait and ongoing therapy that is needed for manufacture of these cells at the commercial level. With this study, the investigators will investigate a new CD19 directed CAR-T therapy that will be manufactured locally with a goal of wider patient inclusion and less delay to CAR-T infusion. The investigators hypothesize that CD19 directed CAR-T cells manufactured using the Prodigy ClinicMACS system developed by Miltenyi (UCD19 CAR-T) will be safe and tolerable and show preliminary efficacy in pediatric patients with relapsed and/or refractory B-ALL or B- NHL

Trial Arms

NameTypeDescriptionInterventions
UCD19 CART infusionExperimentalLymphodepleting chemotherapy following by infusion of UCD19 CAR-T
  • CD19CAR-CD3Zeta-4-1BB-Expressing Allogeneic T-Lymphocyte Cells

Eligibility Criteria

        Inclusion Criteria:

          1. Provision to sign and date the consent form.

          2. Stated willingness to comply with all study procedures and be available for the
             duration of the study.

          3. Males OR non-pregnant, non-lactating females

          4. Aged 30 days to 25 years (inclusive) at time of consent and enrollment

          5. Acute Lymphoid Leukemia OR Non-Hodgkins Lymphoma of B-cell origin that:

               -  Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC),
                  or both

               -  Has relapsed two or more times OR has relapsed at any time after allogeneic BMT
                  OR is refractory to standard therapy as determined by the treating physician

          6. Performance score of 50% or better

        Exclusion Criteria:

          1. Active CNS leukemia or lymphoma

          2. Active Graft-versus-Host Disease (GvHD)

          3. Active, uncontrolled, life threatening infection that at the determination of the
             treating physician would preclude safe apheresis or tolerance of lymphodepleting
             chemotherapy, cell infusion, or cytokine release syndrome

          4. Evidence of severe organ dysfunction that at the determination of the treating
             physician would preclude safe apheresis or tolerance of lymphodepleting chemotherapy,
             cell infusion, or cytokine release syndrome including:

               -  Myocardial dysfunction

               -  Baseline oxygen saturation of < 90% on room air

               -  Diffusion capacity of the lungs for carbon monoxide (DLCO) < 40%

               -  Transaminases > 10x upper limit of normal (ULN) or bilirubin >2x the ULN, unless
                  thought to be related to leukemia/lymphoma infiltration

               -  Estimated Cr clearance <60 mL/min/1.73 m2 (if nuclear medicine GFR or other more
                  specific testing exceeds this level than it can supersede the estimated
                  clearance)

          5. Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to
             use birth control (includes abstinence) for the study duration

          6. Known HIV infection, active Hepatitis B or Hepatitis C infection

          7. Prior gene therapy

          8. Current or prior therapies including:

               -  Monoclonal antibody therapy (i.e. blinatumomab) within 14 days of study
                  enrollment

               -  Immunomodulatory drugs (i.e. tyrosine kinase inhibitors or calcineurin
                  inhibitors) within 14 days of study enrollment

               -  Radiation therapy within 14 days of study enrollment

               -  Corticosteroid therapy in excess of maintenance dosing for adrenal insufficiency
                  within 14 days of study enrollment

               -  Allogeneic blood or marrow transplant within 100 days of study enrollment

               -  Donor lymphocyte infusion or other cellular therapeutic within 30 days of study
                  enrollment
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities
Time Frame:Up to 21 months
Safety Issue:
Description:Adverse events (toxicity assessments) will be done by medical staff at different time points

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:The subject will be followed throughout the study and up to 5 years after the study for overall survival.
Measure:Time to Transplant
Time Frame:5 years
Safety Issue:
Description:The subject will be followed throughout the study and up to 5 years after the study for time to transplant.
Measure:Relapse
Time Frame:5 years
Safety Issue:
Description:The subject will be followed throughout the study and up to 15 years after the study for relapse.
Measure:Non-Relapse Mortality
Time Frame:5 years
Safety Issue:
Description:The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Last Updated

March 23, 2021