NCT02772198

Brief Summary

This phase 1 / 2 study will evaluate the response of B-cell malignancies expressing CD19 to autologous T cells transduced with a second generation anti-CD19 chimeric antigen receptor in children and young adults.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2016

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 9, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 13, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

November 1, 2016

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2022

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

November 3, 2020

Status Verified

October 1, 2020

Enrollment Period

5.7 years

First QC Date

May 9, 2016

Last Update Submit

November 1, 2020

Conditions

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

Outcome Measures

Primary Outcomes (3)

  • Number of patients with treatment related adverse events as assessed by CTCAE v4.

    2 years

  • Overall Response Rate

    Overall response rate = complete response (CR) + partial response (PR) + complete response with incomplete count recovery (CRi) in leukemia patients; Assessment using bone marrow evaluation for patients with leukemia, and imaging (CT / PET CT) for patients with lymphoma

    28 days

  • Feasibility of CD19 CAR T cell production as defined by number of products successfully meeting release criteria

    For each participant, the feasibility of generating sufficient autologous CAR T cells within 12 days will be evaluated.

    12 days

Secondary Outcomes (3)

  • CAR T cell persistence as measured by enumeration of CAR T cells in the blood and bone marrow of participants

    1 year

  • T cell activity and exhaustion profile as measured by flow cytometry

    3 months

  • Cytokine levels in the peripheral blood of the patients

    30 days

Study Arms (1)

Single Arm

EXPERIMENTAL

All patients will be treated on this single arm

Biological: CD19 CAR T cells

Interventions

CD19 CAR T cellsBIOLOGICAL

Autologous T cells activated and transduced with a chimeric antigen receptor targeting CD19

Single Arm

Eligibility Criteria

Age1 Year - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patient with relapsed or refractory B-cell malignancy
  • Age 1-50 years
  • CD19 expression shown by flow cytometry or immunohistochemistry on at least 70% of leukemic blasts / lymphoma cells
  • Adequate CD3 count (above 250 CD3+ cells per microliter blood)
  • Clinical performance status: Patients \> 10 years of age: Karnofsky ≥ 50%; Patients ≤ 10 years of age: Lansky scale ≥ 50%. Exception for neurologic symptoms (e.g. paralysis) that are explained by the malignancy.
  • Females of child-bearing potential must have a negative pregnancy test
  • Cardiac function: Left ventricular ejection fraction \>45% or shortening fraction \>28%
  • For patients following allogeneic bone marrow transplantation - at least 100 days post BMT with no signs or symptoms of active graft-versus-host disease.

You may not qualify if:

  • Hyperleukocytosis (WBC\>50,000) or rapidly progressive disease
  • Pregnant or breast-feeding females
  • Hepatic dysfunction, defined as bilirubin \> x2 upper normal limit (except when explained by hemolysis or Gilbert) or serum glutamate oxaloacetate transaminase \> x25 upper normal limit.
  • Hepatitis B, Hepatitis C or HIV infection.
  • Anti-neoplastic treatment given in the 2 weeks prior to apheresis, with the exception of intrathecal chemotherapy.
  • Active immunosuppressive therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chaim Sheba Medical Center

Ramat Gan, Israel

RECRUITING

Related Publications (5)

  • Itzhaki O, Jacoby E, Nissani A, Levi M, Nagler A, Kubi A, Brezinger K, Brayer H, Zeltzer LA, Rozenbaum M, Vernitsky H, Markel G, Toren A, Avigdor A, Schachter J, Besser MJ. Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. J Immunother Cancer. 2020 Mar;8(1):e000148. doi: 10.1136/jitc-2019-000148.

    PMID: 32152221BACKGROUND

  • Fried S, Avigdor A, Bielorai B, Meir A, Besser MJ, Schachter J, Shimoni A, Nagler A, Toren A, Jacoby E. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019 Oct;54(10):1643-1650. doi: 10.1038/s41409-019-0487-3. Epub 2019 Feb 26.

    PMID: 30809033BACKGROUND

  • Jacoby E, Bielorai B, Avigdor A, Itzhaki O, Hutt D, Nussboim V, Meir A, Kubi A, Levy M, Zikich D, Zeltzer LA, Brezinger K, Schachter J, Nagler A, Besser MJ, Toren A. Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. Am J Hematol. 2018 Dec;93(12):1485-1492. doi: 10.1002/ajh.25274. Epub 2018 Sep 26.

    PMID: 30187944RESULT

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PMID: 34515338DERIVED

  • Nissani A, Lev-Ari S, Meirson T, Jacoby E, Asher N, Ben-Betzalel G, Itzhaki O, Shapira-Frommer R, Schachter J, Markel G, Besser MJ. Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy. J Immunother Cancer. 2021 May;9(5):e001743. doi: 10.1136/jitc-2020-001743.

    PMID: 33990415DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma

Central Study Contacts

Amos Toren, MD,Phd

CONTACT

03-5302934amos.toren@sheba.health.gov.il

Elad Jacoby, MD

CONTACT

03-5302934elad.jacoby@sheba.health.gov.il

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 9, 2016

First Posted

May 13, 2016

Study Start

November 1, 2016

Primary Completion

July 1, 2022

Study Completion

November 1, 2022

Last Updated

November 3, 2020

Record last verified: 2020-10

Locations

IL(1)