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Acute Lymphoblastic Leukemia, B-precursorPhase 1/2NCT02772198

T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies

A Phase 1/2 study testing CD19 CAR T cells in people with Acute Lymphoblastic Leukemia, B-precursor and Non-Hodgkin Lymphoma, B-cell, run by Sheba Medical Center at 1 site in Israel.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 50 years
What is being tested?
CD19 CAR T cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteIsrael
Study dates
Nov 2016to Nov 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Amos Toren, MD,Phd contact

03-5302934

amos.toren@sheba.health.gov.il

Elad Jacoby, MD contact

03-5302934

elad.jacoby@sheba.health.gov.il

Israel1 site, 1 recruiting

  • Chaim Sheba Medical Center

    Ramat Gan

    Diana Bar, +972-3-5303699, Diana.Chigalayev@sheba.health.gov.il

    Elad Jacoby, MD, +972-3-5302934, elad.jacoby@sheba.health.gov.il

    Recruiting

Other trials in Israel

About this study

Official title: A Phase 1 / 2 Single Arm Study of T-cells Expressing Anti-CD19 Chimeric Antigen Receptor in Pediatric and Young Adult Patients With B-cell Malignancies

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.

Read the detailed description

Autologous T cells transduced with chimeric antigen receptors (CAR) that recognize the CD19 antigen (CD19-CAR T cells) have been used in multiple clinical trials at several institutions worldwide. We established an in-house manufacturing process for CD19-CAR T cells with a CD28 (cluster of differentiation 28) costimulatory domain.

Primary Objectives:

  1. To study the safety of administration of CAR T cell at the Sheba Medical Center
  2. To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies.

Secondary Objectives

  1. To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion.
  2. To study the cytokine milieu in CAR treated patients.

Eligibility Patients 1-50 years of age, with a CD19-expressing B-cell malignancy that has recurred after, or not responded to, one or more standard chemotherapy-containing regimens.

Design Peripheral blood mononuclear cells (PBMCs)will be obtained by leukapheresis. Anti-CD19 CAR T cells will be manufactured from fresh autologous PBMCs. PBMC will be cultured in the presence of anti-CD3 (cluster of differentiation 3) antibody and interleukin-2 followed by retroviral vector supernatant containing the anti-CD19 CAR. Total culture time is between 7-10 days. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion, and on day 0 will receive one million CAR T cells per kilogram. Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia; for response of their underlying malignancy; and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).

Being tested
CD19 CAR T cells
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD19 CAR T cellsBiological

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

Study groups in NCT02772198
Study groupRoleWhat they receive
Single ArmExperimentalAll patients will be treated on this single arm
Receives: Biological: CD19 CAR T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 2 years

  2. 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

    Measured: 28 days

  3. 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.

    Measured: 12 days

Secondary outcomes (3)

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

    Enumeration of CAR T cells in the blood and bone marrow of participants

    Measured: 1 year

  2. T cell activity and exhaustion profile as measured by flow cytometry

    Assessment of T cells from peripheral blood by flow cytometry for expression of activation and exhaustion markers.

    Measured: 3 months

  3. Cytokine levels in the peripheral blood of the patients

    Measurement of cytokines in the blood of participants following CAR T cell administration

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionJul 2022 (estimated)
  4. Study completionNov 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02772198
Sponsor's protocol ID
SHEBA-15-2076-AT-CTIL
Status last verified
Oct 2020
First submitted
9 May 2016
Last updated
3 Nov 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 32152221

  • 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.

    PubMed 30809033

  • 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.

    PubMed 30187944

  • Abramovich A, Adam E, Shapira A, Hutt D, Itzhaki O, Bielorai B, Toren A, Jacoby E. CD28-costimulated CD19 CAR-T cells for pediatric mature non-Hodgkin B-cell lymphoma. Bone Marrow Transplant. 2025 Jul;60(7):1045-1051. doi: 10.1038/s41409-025-02615-0. Epub 2025 Apr 23.

    PubMed 40269280

  • 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.

    PubMed 34515338

  • 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.

    PubMed 33990415

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CD19 CAR T cells in people with Acute Lymphoblastic Leukemia, B-precursor and Non-Hodgkin Lymphoma, B-cell, run by Sheba Medical Center at 1 site in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Amos Toren, MD,Phd (03-5302934, amos.toren@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with treatment related adverse events as assessed by CTCAE v4. (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02772198, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2020.

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