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

NCT03467256 | Unknown Phase 1 DMC

• 1 other identifier: NCPHOI-2018-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

B-cell Acute Lymphoblastic Leukemia; Acute Lymphocytic Leukemia, Pediatric

Outcome Measures

Primary Outcomes (5)

• 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

  1 month

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

  incidence of grade 3-4 Severe Cytokine Release Syndrome

  1 month

• 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

  1 month

• Proportion of patients in MRD-negative remission

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

  1 month

• Proportion of patients in hematologic remission

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

  1 months

Secondary Outcomes (4)

• Duration of MRD-negative remission

  2 years

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

  2 years

• Duration of B-cell aplasia

  5 years

• Overall survival

  5 years

Study Arms (1)

experimental

EXPERIMENTAL

Patients 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.

Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Tocilizumab; Drug: Cytarabine; Drug: Etoposide; Drug: Dexamethasone

Interventions

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

anti-CD19 chimeric antigen receptor - transduced T-cell given IV

experimental

Fludarabine DRUG

given IV

experimental

Cyclophosphamide DRUG

given IV

experimental

Tocilizumab DRUG

given IV

experimental

Cytarabine DRUG

given IV

experimental

Etoposide DRUG

given IV

experimental

Dexamethasone DRUG

given IV

experimental

Eligibility Criteria

• Age: 3 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• \<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)
• 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

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

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

Moscow, 117198, Russia

Location

Related Publications (1)

• 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.

  PMID: 34893603 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy, Adoptive; fludarabine; Cyclophosphamide; tocilizumab; Cytarabine; Etoposide; Dexamethasone

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Design

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

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 15, 2018
• Study Start: May 14, 2018
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2025
• Last Updated: February 24, 2023

Record last verified: 2023-02

Locations

RU (1)