AzTrials
AzTrials

B-cell Acute Lymphoblastic LeukemiaPhase 1/2NCT03467256

CD19 T-CAR for Treatment of Children and Young Adults With r/r B-ALL

A Phase 1/2 study testing Chimeric Antigen Receptor T-Cell Therapy, Fludarabine and Cyclophosphamide in people with B-cell Acute Lymphoblastic Leukemia and Acute Lymphocytic Leukemia, Pediatric, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

Trial summary

The purpose of this study is to evaluate the safety and efficiency of autologous CD19 CAR-T lymphocytes in a cohort of pediatric and young adult patients with relapsed /refractory B-lineage acute lymphoblastic leukemia Read more about this study

Who is it for?
Ages 3 months to 25 years
What is being tested?
Chimeric Antigen Receptor T-Cell Therapy, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteRussia
Study dates
14 May 2018to 15 Oct 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 3 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent
  • Patients with relapsed or refractory CD19-expressing B cell ALL :
  • Induction failure, no CR after course 2 or MRD>0,1% after 3 courses of high-risk protocol
  • early bone marrow or combined relapse of acute lymphoblastic leukaemia, no CR or MRD>0,1% after 1 course 2-nd line therapy
  • ALL post ≥ 2nd relapse, no CR or MRD>0,1% after 1 course 2-nd line therapy
  • Relapse or MRD >0,1% of ALL after stem cell transplant (> 60 days post alloHSCT)
Show all 16Show fewer
  • Late bone marrow or combined relapse of acute lymphoblastic leukaemia, no CR or MRD>0,1% after 2nd course of 2-nd line therapy
  • There must be no available alternative curative therapies
  • CD19 expression must be detected on greater than 30% by flow cytometry
  • Patients must have measurable or evaluable disease at the time of enrolment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
  • Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%
  • Patient Life Expectancy > 8 weeks
  • Patients recovered from acute toxic effects of all prior chemotherapy, immuno- or radiotherapy
  • Patient absolute lymphocyte N > or =100/mm3
  • Patient cardiac function: left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
  • Patients who agree to long-term follow up for up to 5 years (if received CD19 CAR-T cell infusion)

Who cannot join

  • <30% expression of CD19 on the leukemic population
  • Active hepatitis B, C or HIV infection
  • Oxygen saturation < or = 90%
  • Bilirubin >3x upper norma limit
  • Creatinine >3x upper norma limit
  • Active acute GVHD overall grade ≥2 (Seattle criteria)
Show all 10Show fewer
  • Moderate/severe chronic GVHD (NIH consensus) requiring systemic steroids
  • Clinical signs of grade >3 CNS disorders (seizure disorder, paresis, aphasia, cerebrovascular, ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
  • Pregnant or lactating women.
  • Active severe infection

Trial locations and contacts

1 site in 1 country.

Russia1 site

  • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

    Moscow, 117198

Other trials in Russia

About this study

Official title: A Single-Arm Phase I/II Study Evaluating the Safety and Clinical Efficacy Of the 2-nd Generation CD19 Autologous CAR T Cells on the CliniMACS Prodigy Automated Manufacturing Platform in Treatment of Paediatric And Young Adult Patients With Relapsed/Refractory B-lineage Acute Lymphoblastic Leukemia

The purpose of this study is to evaluate the safety and efficiency of autologous CD19 CAR-T lymphocytes in a cohort of pediatric and young adult patients with relapsed /refractory B-lineage acute lymphoblastic leukemia

Read the detailed description

The main objectives of the study are:

  1. To investigate the safety of auto-CD19 CAR T-cells therapy among children and young adults with refractory/relapsed B-cell ALL on the basis of prospective evaluation of adverse affects frequency and severity according to CTCAE v.4
  2. To study the efficacy of auto-CD19 CAR T-cells therapy among children and young adults with refractory/relapsed B-cell ALL on the basis of proportion of patients in haematological and molecular remission at 28 days after infusion.
  3. To evaluate long-term efficacy of auto-CD19 CAR T-cells therapy among children and young adults with refractory/relapsed B-cell ALL on the basis of overall and event-free survival at 1 and 3 years after infusion.

The novelty of this study will be cytokine release syndrome prophylaxis by tocilizumab Patients will receive fludarabine 120 mg/m2 (totally) intravenously (IV) over 30 minutes on days -5 to -2 and cyclophosphamide 750 mg/m2 IV over 60 minutes on day -2. One hour prior to infusion of CAR T-cells patients will receive tocilizumab IV 8 mg/kg (max 800 mg) over 1 hour. Patients then receive CD19-CAR T cells IV over 20-30 minutes on day 0.

This is a dose-escalation study of CD19-CAR T cells. Dose escalation consistently:

  • Level 1 5х105/kg CD19 CAR-T lymphocytes
  • Level 2 1х106/kg CD19 CAR-T lymphocytes
  • Level 3 3х106/kg CD19 CAR-T lymphocytes
  • Level 0 1х105/kg CD19 CAR-T lymphocytes (in case of dose-limiting toxicity at dose Level 1) In case of severe side affects next dose will be reduced to the previous lower dose.

Based on interim analysis the following dosing approach based on stratification by the initial leukemia burden will be implemented starting November 2019:

  • Patients with low disease burden (<15% blast cells in BM) will receive a lymphodepletion chemotherapy of fludarabine IV (total dose 120mg/m2) and cyclophosphamide IV (total dose 750mg/m2) over 5 days.

CD19 CAR-T cells will be infused IV in dose 1x106/kg on day 0.

  • Patients will high disease burden (>15% blast cells in BM) will receive a lymphodepletion chemotherapy of fludarabine IV (total dose 120 mg/m2), cyclophosphamide IV (total dose 750 mg/m2), cytarabine IV (total dose 900 mg/m2), etoposide IV (total dose 450 mg/m2), dexamethasone IV (total dose 30 mg/m2) over 5 days.

CD19 CAR-T cells 1st dose will be infused IV on day 0 - 0,1x106/kg, 2nd dose will be infused IV between day 7 and 14 - 0,9x106/kg.

Being tested
Chimeric Antigen Receptor T-Cell Therapy, Fludarabine, Cyclophosphamide, Tocilizumab, Cytarabine
Medical subject headings
Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

Study groups in NCT03467256
Study groupRoleWhat they receive
experimentalExperimentalPatients will receive lymphodepleting chemotherapy, one hour prior to infusion of CAR T-cells patients will receive tocilizumab IV 8 mg/kg (max 800 mg) over 1 hour. Patients then receive CD19-CAR T cells IV on day 0.
Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Tocilizumab; Drug: Cytarabine; Drug: Etoposide; Drug: Dexamethasone

What is being measured

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

  1. Incidence of grade 3-5 SAE occurring within 30 days of CD19CAR T-cell infusion

    incidence of grade 3-5 SAE according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 occurring within 30 days of CD19CAR T-cell infusion

    Measured: 1 month

  2. Incidence of grade 3-4 Severe Cytokine Release Syndrome following CD19 CAR T-cell infusion

    incidence of grade 3-4 Severe Cytokine Release Syndrome

    Measured: 1 month

  3. Incidence of grade 3-5 neurotoxicity occurring within 30 days of CD19 CAR T-cell infusion

    incidence of grade 3-5 neurotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 occurring within 30 days of CD19 CAR T-cell infusion

    Measured: 1 month

  4. Proportion of patients in MRD-negative remission

    Proportion of patients in MRD-negative remission among all enrolled patients

    Measured: 1 month

  5. Proportion of patients in hematologic remission

    Proportion of patients in hematologic remission among all patients with morphological disease (NO CR) at enrollment

    Measured: 1 months

Secondary outcomes (4)

  1. Duration of MRD-negative remission

    Duration of MRD-negative remission

    Measured: 2 years

  2. Persistence/frequency of CD19 CAR T lymphocytes in peripheral (FC+qPCR)

    Persistence/frequency of CD19 CAR T lymphocytes in peripheral (FC+qPCR)

    Measured: 2 years

  3. Duration of B-cell aplasia

    Duration of B-cell aplasia and hypogammaglobulinemia, time 0 - day of CD19-CAR T cells infusion

    Measured: 5 years

  4. Overall survival

    the probability of survival, time 0 - day of CD19-CAR T cells infusion

    Measured: 5 years

Timeline

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

  1. First posted15 Mar 2018
  2. Study start14 May 2018
  3. Primary completion15 Oct 2020
  4. Study completion15 Oct 2025 (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
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03467256
Sponsor's protocol ID
NCPHOI-2018-01
Status last verified
Feb 2023
First submitted
9 Mar 2018
Last updated
24 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Maschan M, Caimi PF, Reese-Koc J, Sanchez GP, Sharma AA, Molostova O, Shelikhova L, Pershin D, Stepanov A, Muzalevskii Y, Suzart VG, Otegbeye F, Wald D, Xiong Y, Wu D, Knight A, Oparaocha I, Ferencz B, Roy A, Worden A, Kruger W, Kadan M, Schneider D, Orentas R, Sekaly RP, de Lima M, Dropulic B. Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients. Nat Commun. 2021 Dec 10;12(1):7200. doi: 10.1038/s41467-021-27312-6.

    PubMed 34893603

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Chimeric Antigen Receptor T-Cell Therapy, Fludarabine and Cyclophosphamide in people with B-cell Acute Lymphoblastic Leukemia and Acute Lymphocytic Leukemia, Pediatric, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.

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 16 inclusion and 10 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 24 Feb 2023. 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 Russia. 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?

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?

Incidence of grade 3-5 SAE occurring within 30 days of CD19CAR T-cell infusion (time frame: 1 month). The study lists 5 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 NCT03467256, 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 24 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in