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

Primary Purpose

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

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

About this trial

This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia

Eligibility Criteria

30 Days - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provision to sign and date the consent form.
Stated willingness to comply with all study procedures and be available for the duration of the study.
Males OR non-pregnant, non-lactating females
Aged 30 days to 25 years (inclusive) at time of consent and enrollment
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
Performance score of 50% or better

Exclusion Criteria:

Active CNS leukemia or lymphoma
Active Graft-versus-Host Disease (GvHD)
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
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)
Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration
Known HIV infection, active Hepatitis B or Hepatitis C infection
Prior gene therapy
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

Sites / Locations

Children's Hospital ColoradoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

UCD19 CART infusion

Arm Description

Lymphodepleting chemotherapy following by infusion of UCD19 CAR-T

Outcomes

Primary Outcome Measures

Dose limiting toxicities

Adverse events (toxicity assessments) will be done by medical staff at different time points

Secondary Outcome Measures

Overall Survival

The subject will be followed throughout the study and up to 5 years after the study for overall survival.

Time to Transplant

The subject will be followed throughout the study and up to 5 years after the study for time to transplant.

Relapse

The subject will be followed throughout the study and up to 15 years after the study for relapse.

Non-Relapse Mortality

The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality

Full Information

NCT ID

NCT04544592

First Posted

May 29, 2019

Last Updated

November 9, 2022

Sponsor

University of Colorado, Denver

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04544592

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)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 24, 2021 (Actual)

Primary Completion Date

June 2026 (Anticipated)

Study Completion Date

July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

UCD19 CART infusion

Arm Type

Experimental

Arm Description

Lymphodepleting chemotherapy following by infusion of UCD19 CAR-T

Intervention Type

Drug

Intervention Name(s)

CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

Intervention Description

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 Measure Information:

Title

Dose limiting toxicities

Description

Adverse events (toxicity assessments) will be done by medical staff at different time points

Time Frame

Up to 21 months

Secondary Outcome Measure Information:

Title

Overall Survival

Description

The subject will be followed throughout the study and up to 5 years after the study for overall survival.

Time Frame

5 years

Title

Time to Transplant

Description

The subject will be followed throughout the study and up to 5 years after the study for time to transplant.

Time Frame

5 years

Title

Relapse

Description

The subject will be followed throughout the study and up to 15 years after the study for relapse.

Time Frame

5 years

Title

Non-Relapse Mortality

Description

The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Days

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision to sign and date the consent form. Stated willingness to comply with all study procedures and be available for the duration of the study. Males OR non-pregnant, non-lactating females Aged 30 days to 25 years (inclusive) at time of consent and enrollment 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 Performance score of 50% or better Exclusion Criteria: Active CNS leukemia or lymphoma Active Graft-versus-Host Disease (GvHD) 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 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) Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration Known HIV infection, active Hepatitis B or Hepatitis C infection Prior gene therapy 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amy Keating, MD

Phone

720-777-6740

amy.keating@ucanschutz.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Verneris, MD

michael.verneris@cunaschutz.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amy Keating, MD

Organizational Affiliation

Children's Hospital Colorado

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alison Sutton

Phone

720-777-9920

Alison.Sutton@childrenscolorado.org

First Name & Middle Initial & Last Name & Degree

Amy Keating

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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