UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicities [Up to 21 months]
Adverse events (toxicity assessments) will be done by medical staff at different time points
Secondary Outcome Measures
- Overall Survival [5 years]
The subject will be followed throughout the study and up to 5 years after the study for overall survival.
- Time to Transplant [5 years]
The subject will be followed throughout the study and up to 5 years after the study for time to transplant.
- Relapse [5 years]
The subject will be followed throughout the study and up to 15 years after the study for relapse.
- Non-Relapse Mortality [5 years]
The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision to sign and date the consent form.
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Stated willingness to comply with all study procedures and be available for the duration of the study.
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Males OR non-pregnant, non-lactating females
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Aged 30 days to 25 years (inclusive) at time of consent and enrollment
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Acute Lymphoid Leukemia OR Non-Hodgkins Lymphoma of B-cell origin that:
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Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC), or both
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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
- Performance score of 50% or better
Exclusion Criteria:
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Active CNS leukemia or lymphoma
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Active Graft-versus-Host Disease (GvHD)
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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
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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:
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Myocardial dysfunction
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Baseline oxygen saturation of < 90% on room air
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Diffusion capacity of the lungs for carbon monoxide (DLCO) < 40%
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Transaminases > 10x upper limit of normal (ULN) or bilirubin >2x the ULN, unless thought to be related to leukemia/lymphoma infiltration
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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)
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Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration
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Known HIV infection, active Hepatitis B or Hepatitis C infection
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Prior gene therapy
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Current or prior therapies including:
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Monoclonal antibody therapy (i.e. blinatumomab) within 14 days of study enrollment
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Immunomodulatory drugs (i.e. tyrosine kinase inhibitors or calcineurin inhibitors) within 14 days of study enrollment
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Radiation therapy within 14 days of study enrollment
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Corticosteroid therapy in excess of maintenance dosing for adrenal insufficiency within 14 days of study enrollment
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Allogeneic blood or marrow transplant within 100 days of study enrollment
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Donor lymphocyte infusion or other cellular therapeutic within 30 days of study enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
Sponsors and Collaborators
- University of Colorado, Denver
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Amy Keating, MD, Children's Hospital Colorado
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18-2424.cc
- P30CA046934