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CD19-ALLPhase 1/2NCT03373071

Anti-CD19 CAR T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and NHL

A Phase 1/2 study testing CD19-CAR T cell in people with CD19-ALL and CD19-LNH, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this phase I study is to evaluate the safety and to establish the recommended dose of CD19-CART01 infused in pediatric patients affected by relapsed/refractory B-ALL or NHL with measurable Bone Marrow (BM) involvement. Read more about this study

Who is it for?
Ages 6 months to 25 years
Conditions the study is for
CD19-ALL, CD19-LNH
What is being tested?
CD19-CAR T cell
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteItaly
Study dates
23 Dec 2017to 24 Jan 2025
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 6 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Male and female subjects with CD19 expressing B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin Lymphoma (NHL) with BM involvement and one of the following:
  • Patients in 2nd or subsequent relapse, after at least one standard frontline chemotherapy and one salvage regimen, with BM involvement ii. Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there is no evidence of active GVHD and if the patient is no longer taking immunosuppressive agents for at least 30 days prior to enrollment iii. MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
  • Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease, including MRD detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
  • Age: 6 months - 25 years.
  • Voluntary informed consent is given. For subjects < 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
  • Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
  • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
  • Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.

Who cannot join

  • Pregnant or lactating women
  • Severe, uncontrolled active intercurrent infections
  • HIV, or active HCV and/or HBV infection
  • Life-expectancy < 6 weeks
  • Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN
  • Renal function: serum creatinine > 3x ULN for age.
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  • Blood oxygen saturation < 90%.
  • Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
  • Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
  • BM blasts > 50% pre-infusion.
  • Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy
  • Active CNS disease as documented by the presence of blasts in the CSF or by MRI. This criterion could be revised once that, after the phase I portion of the study, absence of life-threatening (i.e. grade IV) neurological toxicity will be documented.
  • Presence of active, grade 2-4 acute or extensive chronic GvHD
  • Recurrent or refractory ALL with testicular involvement
  • Concurrent or recent prior therapies, before infusion:
  • Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.
  • Systemic chemotherapy in the 2 weeks preceding infusion. iii. Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 4 weeks preceding infusion.
  • Immunosuppressive agents in the 2 weeks preceding infusion. v. Radiation therapy must have been completed at least 3 weeks prior to enrollment.
  • Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);
  • Exceptions:
  • There is no time restriction with respect to prior intrathecal chemotherapy, provided that there is complete recovery from any acute toxic effects of such;
  • Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided that they meet all other eligibility criteria;
  • Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase in dose for at least 2 weeks prior to starting apheresis;
  • Patient-derived CD19-CART01 production failure

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale Pediatrico Bambino Gesù

    Roma

Other trials in Italy

About this study

Official title: Phase I/II Study of Anti-CD19 Chimeric Antigen Receptor-Expressing T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia and Non Hodgkin Lymphoma

The primary objective of this phase I study is to evaluate the safety and to establish the recommended dose of CD19-CART01 infused in pediatric patients affected by relapsed/refractory B-ALL or NHL with measurable Bone Marrow (BM) involvement. The phase II extension is aimed at testing the efficacy of the treatment at the optimal dose defined in the phase I.

Read the detailed description

The study will consist of 2 phases, a Phase I or dose escalation phase and a Phase II or expansion phase. Paediatric/young adult patients with relapsed or refractory B cell ALL will be enrolled. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture. Autologous CAR T product directed against CD19-expressing tumor cells (CD19-CART01) will be produced and, after a lymphodepletion with conventional chemoterapic agents, the patient will receive CD19-CART01 intravenously. The construct contains also the suicide gene safety switch "inducible Caspase 9"; therefore, in case of relevant toxicities, the patient will receive the dimerizing agent in order to induce the apoptosis of the cells.

After the treatment, the patients will then enter a 36-month follow-up period.

Conditions
CD19-ALL, CD19-LNH
Being tested
CD19-CAR T cell
Keywords
CD19-CAR T cell, CD19-malignancy, CAR T cell, CD19-ALL, CD19-LNH

What participants receive

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

  • CD19-CAR T cellBiological

    Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with 0.5 to 3.0 x 10⁶/kg CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.

    In case of toxicity, the patient will receive the dimerizing drug activating the suicide safety switch in order to improve the safety of the treatment

Study groups in NCT03373071
Study groupRoleWhat they receive
CD19-CART01ExperimentalFollowing the lymphodepleting treatment, with patients will be treated with 0.5 to 3.0 x 10⁶/kg CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose
Receives: Biological: CD19-CAR T cell

What is being measured

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

  1. Phase I - Identification of the dose limiting toxicity (DLT)

    Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 4 and the number of patients experiencing DLT will be evaluated

    Measured: 4 weeks after CAR T cell infusion

  2. Phase II - Efficacy

    Complete remission rate minimal residual disease (MRD) negative response

    Measured: 4 weeks after CAR T cell infusion

Secondary outcomes (8)

  1. Overall Response Rate (ORR)

    Assessment of CR with incomplete blood count recovery (CRi), Partial Response (PR) and Stable Disease (SD).

    Measured: 4 weeks after CAR T cell infusion

  2. In vivo persistence/expansion of infused CAR T cell

    Detection of infused CAR T cell in the peripheral and bone marrow blood

    Measured: Up to 5 years

  3. Function of infused CAR T cell

    Assessment through functional assays (such as ELISPOT for interferon-gamma release using CD19-positive cells and CD19-negative target cells) and immunophenotyping on peripheral blood mononuclear cells (PBMCs) isolated from the patients

    Measured: Up to 5 years

  4. Cytokine profiling

    Define serum cytokine profile after T cell infusion and correlation with cytokine release syndrome (CRS)

    Measured: 10 days after CAR T cell infusion

  5. Disease Outcome

    Assessment of relapse rate

    Measured: Up to 3 years

  6. Overall Survival

    Measured: Up to 3 years

  7. Disease-free survival

    Measured: Up to 3 years

  8. Elimination of CAR T cell in case of toxicity

    Assessment the kinetics of CAR T cells elimination after AP1903 infusion

    Measured: Up to 15 years

Timeline

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

  1. First posted14 Dec 2017
  2. Study start23 Dec 2017
  3. Primary completion11 May 2021
  4. Study completion24 Jan 2025

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
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03373071
Sponsor's protocol ID
CD19-CAR01
Status last verified
Feb 2025
First submitted
6 Dec 2017
Last updated
5 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CD19-CAR T cell in people with CD19-ALL and CD19-LNH, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.

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 24 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: finished, as of the sponsor's last update on 5 Feb 2025. 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 Italy. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - Identification of the dose limiting toxicity (DLT) (time frame: 4 weeks after CAR T cell infusion). The study lists 2 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 NCT03373071, which also lists 1 linked publication.

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 5 Feb 2025.

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