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

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ClinicalTrials.gov Identifier: NCT04544592
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : August 30, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.

Condition or disease Intervention/treatment Phase
B-cell Acute Lymphoblastic Leukemia B-cell Non Hodgkin Lymphoma Drug: CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells Phase 1 Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 24, 2021
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : July 2026


Arm Intervention/treatment
Experimental: UCD19 CART infusion
Lymphodepleting chemotherapy following by infusion of UCD19 CAR-T
Drug: CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells
The CD19 CAR used in this study consists of three main components: the variable regions of the anti-CD19 monoclonal antibody FMC63 71, linked to the TNFRSF19-derived transmembrane domain, the 4-1BB costimulatory molecule, and the signaling domain of the CD3-zeta molecule. The DNA encoding this receptor was cloned into a lentiviral vector (LV) backbone.




Primary Outcome Measures :
  1. Dose limiting toxicities [ Time Frame: Up to 21 months ]
    Adverse events (toxicity assessments) will be done by medical staff at different time points


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 5 years ]
    The subject will be followed throughout the study and up to 5 years after the study for overall survival.

  2. Time to Transplant [ Time Frame: 5 years ]
    The subject will be followed throughout the study and up to 5 years after the study for time to transplant.

  3. Relapse [ Time Frame: 5 years ]
    The subject will be followed throughout the study and up to 15 years after the study for relapse.

  4. Non-Relapse Mortality [ Time Frame: 5 years ]
    The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04544592


Contacts
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Contact: Amy Keating, MD 720-777-6740 amy.keating@ucdenver.edu
Contact: Cheri Adams Cheri.Adams@childrenscolorado.org

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Courtney Newbold    720-848-0653    courtney.newbold@childrenscolorado.edu   
Principal Investigator: Amy Keating         
Sponsors and Collaborators
University of Colorado, Denver
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amy Keating, MD Children's Hospital Colorado
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04544592    
Other Study ID Numbers: 18-2424.cc
P30CA046934 ( U.S. NIH Grant/Contract )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases