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B-ALLPhase 1/2NCT04499573

Bispecific CD19/CD22 CAR-T for Treatment of Children and Young Adults With r/r B-ALL

A Phase 1/2 study testing CD19/CD22 CAR-T in people with B-ALL, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and efficiency of autologous CD19/CD22 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
Conditions the study is for
B-ALL
What is being tested?
CD19/CD22 CAR-T
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteRussia
Study dates
27 Jul 2020to 13 Mar 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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
  • CD19 or CD22 expression must be detected on greater than 50% of leukemic cells by flow cytometry
  • Presence of a measurable mass of tumor cells in the bone marrow or extramedullary sites at the time of patient's inclusion in the study
  • Patients with relapsed or refractory CD19 and CD22-expressing B-cell ALL:
  • Induction failure
  • MRD ≥ 0,1% after 2nd chemotherapy course for high-risk group patients.
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  • First bone marrow or combined relapse of acute lymphoblastic leukemia, no CR or MRD ≥ 0,1% after 1-course 2nd line therapy
  • Second and further relapse of ALL
  • Relapse or MRD ≥ 0,1% of ALL after hematopoietic stem cell transplant (> 60 days post alloHSCT)o There must be no available alternative approved curative therapies
  • Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%
  • Patient Life Expectancy > 4 weeks
  • Patients recovered from acute toxic effects of prior chemotherapy, immune- or radiotherapy
  • Patient absolute blood naïve (CD45RA+) T-lymphocyte count ≥ 50/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/CD22 CAR-T cell infusion)
  • March 2021 amendment: Healthy HLA-matched related or haploidentical donor (only for HSCT cohort)

Who cannot join

  • <50% expression of both CD19 and CD22 on the leukemic population
  • Active (detectable viremia) hepatitis B, C or HIV infection
  • Oxygen saturation ≤ 90%
  • Bilirubin >3x upper norma limit
  • Creatinine >3x upper norma limit
  • Active acute GVHD overall grade ≥2 (Seattle criteria)
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  • 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 (unresolved) severe infection

Trial locations and contacts

1 site in 1 country.

Russia1 site

  • Federal Research Institute of Pediatric Hematology, Oncology and Immunology

    Moscow, 117198

Other trials in Russia

About this study

Official title: Safety and Efficiency of Anti-CD19/CD22 Tandem Fully Human Chimeric Antigen Receptor (CAR)-Transduced T-cell Therapy for Pediatric and Young Adult Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia: a Single Centre, Non-randomised, Open Label Phase I-II Clinical Trial of Automatically Produced Cell Therapy Product MB-CAR-T19-22 Using CliniMACS Prodigy

The purpose of this study is to evaluate the safety and efficiency of autologous CD19/CD22 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:

  • To investigate the incidence of adverse events of grade 3-5 within after CD19/CD22 CAR lymphocyte infusion by day 28,
  • To evaluate the incidence of complete remission and MRD-negative CR by day 28
  • To evaluate the long-term effectiveness of CD19/CD22 CAR-T therapy (cumulative incidence of relapse, event-free survival, overall survival) at 1, 2, and 5 years after infusion.
  • To evaluate the persistence of CD19/CD22 CAR-T cells and duration of B-cell aplasia (<1% B-cells in the blood) and hypogammaglobulinemia In order to prevent the development of CRS, all patients will receive an infusion of tocilizumab at 8 mg/kg body weight on day 0 before CAR-T cells infusion.

Step-down and step-up dosing will be used to adapt the trial to the scenario of excess toxicity and/or suboptimal effect. Reevaluation of dosing will be done for each cohort separately after the enrollment 5th study subject reaches day 28 or earlier if the threshold for excess toxicity or suboptimal effect is achieved.

Based on interim analysis in March 2021 after the enrollment 5th study subject reaches day 28 study population will be divided into three cohorts:

  1. CD19-positive (both CD19 and CD22 expressed on over 50% of leukemia cells), low and high disease burden.
  2. CD19-negative (CD22 expressed on over 50% of leukemia cells) low and high disease burden;
  3. Allogeneic HSCT+ allogeneic CAR-T cohort
Conditions
B-ALL
Being tested
CD19/CD22 CAR-T
Keywords
B-ALL, acute lymphoblastic leukemia, CAR-T
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • CD19/CD22 CAR-TDrug

    Also called Fludarabine, Cyclophosphamide, Cytarabine, Etoposide

    The treatment plan will be based on stratification by the initial leukemia burden.

    Patients with "low disease burden" will receive a lymphodepletion chemotherapy of fludarabine (total dose 120mg/m2) and cyclophosphamide (total dose 750mg/m2) over 5 days.

    Patients will "high disease burden" will receive a lymphodepletion chemotherapy of fludarabine (total dose 120 mg/m2), cyclophosphamide (total dose 750 mg/m2), cytarabine (total dose 900 mg/m2), etoposide (total dose 450 mg/m2), dexamethasone (total dose 30 mg/m2) over 5 days.

    Based on interim analysis the following dosing approach will be implemented starting April 2021:

    Cohort 1: CD19+ disease, low and high burden: 1st dose - 150k/kg, 2nd dose - 850k/kg Cohort 2: CD19- disease, low and high burden: 1st dose - 500k/kg, 2nd dose - 500k/kg Cohort 3: HSCT+CAR-T: 100k/kg

Study groups in NCT04499573
Study groupRoleWhat they receive
intervention/treatmentExperimentalIntervention: 1. Patient (cohort 1 and 2) or donor (cohort 3) leukapheresis 2. Drug therapy: * Fludarabine 120 mg/m2 * Cyclophosphamide 750 mg/m2 * Etoposide 450 mg/m2 * Cytarabine 900 mg/m2 * Dexamethasone 30 mg/m2 * Tocilizumab 8 mg/kg BW 3. Biological: Cohort 1 and 2: autologous CD19/CD22 CAR-T lymphocytes, dose 0.15 - 1.5х106/kg Cohort 3: allogeneic CD19/CD22 CAR-T lymphocytes, dose 0.1х106/kg + allogeneic HSCT from a haploidentical or matched related donor
Receives: Drug: CD19/CD22 CAR-T

What is being measured

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

  1. incidence of grade 3-5 SAE

    Safety:

    Toxicity evaluation following CD19/CD22 CAR T-cell infusion:

    • incidence of grade 3-5 SAE (according CTCAE v.5.0)

    Measured: 1 month

  2. incidence of grade 3-5 Severe Cytokine Release Syndrome

    Safety:

    Toxicity evaluation following CD19/CD22 CAR T-cell infusion:

    • incidence of grade 3-5 Severe Cytokine Release Syndrome (according ASTCT consensus)

    Measured: 1 month

  3. incidence of grade 3-5 ICANS

    Safety:

    Toxicity evaluation following CD19/CD22 CAR T-cell infusion:

    • incidence of grade 3-5 ICANS (according to ASTCT consensus)

    Measured: 1 month

  4. Rate of complete remission

    Efficacy:

    • Rate of complete remission among all enrolled patients (Intent-to-Treat population)

    Measured: 1 month

  5. Rate of MRD-negative remission

    Efficacy:

    • Rate of MRD-negative remission among all patients (Intent-to-treat population)

    Measured: 1 month

  6. March 2021 amendment: incidence of graft failure before day 100 (only for HSCT cohort)

    Safety:

    Measured: 100 days

  7. March 2021 amendment: incidence of aGVHD grade 2-4 (only for HSCT cohort)

    Safety:

    Measured: 100 days

Secondary outcomes (6)

  1. Duration of MRD-negative remission

    Efficacy:

    Measured: 2 years

  2. Persistence/frequency of CD19/CD22 lymphocytes in peripheral blood (flow cytometry)

    Efficacy:

    Measured: 2 years

  3. Duration of B-cell aplasia and hypogammaglobulinemia

    Efficacy:

    Measured: 2 years

  4. Overall survival

    Efficacy:

    Measured: 5 years

  5. Safety and adverse effects long-term

    Safety:

    Measured: 5 years

  6. March 2021 amendment: Incidence of chronic GVHD (only for HSCT cohort)

    Safety:

    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 posted5 Aug 2020
  2. Study start27 Jul 2020
  3. Primary completion13 Mar 2022
  4. Study completion13 Mar 2027 (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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04499573
Sponsor's protocol ID
NCPHOI-2020-07
Status last verified
Feb 2023
First submitted
31 Jul 2020
Last updated
22 Feb 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CD19/CD22 CAR-T in people with B-ALL, 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: under way, not looking for participants, as of the sponsor's last update on 22 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?

This study is still under way. Results are not available in the source record yet.

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 (time frame: 1 month). The study lists 7 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 NCT04499573.

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 22 Feb 2023.

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