CD19-targeting, 3rd Generation CAR T Cells for Refractory... | NCT03068416

Studies
CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy

NCT03068416

Sponsor

Uppsala University

Status

Completed

Last Update Posted

Oct 20, 2021Actual

Enrollment

24Actual

Phase

Phase 2

Conditions

B-cell Leukemia
B-Cell Lymphoma

Interventions

CAR T cells

Countries

Sweden

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
2016-004043-36	EudraCT Number

Status Module

Record Verification Date

Oct 2021

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Sep 18, 2017Actual

Primary Completion Date

Aug 19, 2021Actual

Completion Date

Aug 19, 2021Actual

First Submitted Date

Feb 21, 2017

First Submission Date that Met QC Criteria

Feb 24, 2017

First Posted Date

Mar 1, 2017Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 14, 2021

Last Update Posted Date

Oct 20, 2021Actual

Name	Class
Uppsala University Hospital	OTHER
AFA Insurance	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief Summary

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy.

Detailed Description

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Primary outcome:

- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.

Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Secondary outcome:

Tumor response, CAR T cell persistence and immunological profile

Determination of tumor size and the tumor marker CD19.
Determination of the levels of circulating B cells.
Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
Determination of activation markers on CAR T cells such as CD107a.
Determination of the presence of immunological markers in blood and biopsies.

At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

24Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CAR T cells	Experimental	Autologous 3rd generation CD19-targeting CAR T cells	Biological: CAR T cells

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CAR T cells	Biological	Autologous CD19-targeting, 3rd generation CAR T cells	CAR T cells

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months

Secondary Outcomes

Measure	Description	Time Frame
Tumor response	Determination of tumor size	24 months.
B cell levels	Determination of circulating CD19+ B cells	24 months

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
Measurable disease.
All ages
Performance status ECOG 0-2.
Fertile females/males must consent to use contraceptives during participation of the trial.
Signed informed consent.

Exclusion Criteria:

Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
Patients with primary CNS lymphoma.
Known human immunodeficiency virus (HIV) infection.
Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to perform the treatment.
Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest.
Pregnancy
Patients that do not consent to that tissue and blood samples are stored in a biobank
Patients whose cells cannot be manufactured.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

0 Years

Maximum Age

100 Years

Standard Ages

ChildAdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Gunilla Enblad, MD, PhD	Uppsala University Hospital, Dept of Oncology	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Uppsala University Hospital, Dept of Oncology		Uppsala		75185	Sweden

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37540566	Derived	Saren T, Ramachandran M, Gammelgard G, Lovgren T, Mirabello C, Bjorklund AK, Wikstrom K, Hashemi J, Freyhult E, Ahlstrom H, Amini RM, Hagberg H, Loskog A, Enblad G, Essand M. Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients. Clin Cancer Res. 2023 Oct 13;29(20):4139-4152. doi: 10.1158/1078-0432.CCR-23-0178.

ID	Term
D015448	Leukemia, B-Cell
D016393	Lymphoma, B-Cell

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D019264	Adoptive Transfer
D007116	Immunization, Passive
D007114	Immunization
D007167	Immunotherapy