Clinical Trials /

Phase I/II Study Evaluating AUTO4 in Patients With TRBC1 Positive T Cell Lymphoma

NCT03590574

Description:

The purpose of this study is to test the safety and efficacy of AUTO4 a CAR T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin Lymphoma.

Related Conditions:
  • T-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study Evaluating AUTO4 in Patients With TRBC1 Positive T Cell Lymphoma
  • Official Title: A Single Arm, Open Label, Multi-centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO4, a CAR T-cell Treatment Targeting TRBC1, in Patients With Relapsed or Refractory TRBC1 Positive Selected T Cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: AUTO-TL1
  • SECONDARY ID: 2017-001965-26
  • NCT ID: NCT03590574

Conditions

  • T Cell Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Angioimmunoblastic T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma

Interventions

DrugSynonymsArms
AUTO4AUTO4

Purpose

The purpose of this study is to test the safety and efficacy of AUTO4 a CAR T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin Lymphoma.

Detailed Description

      The study will consist of 2 phases, a Phase I or dose escalation phase and a Phase II or
      expansion phase. Patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin
      Lymphoma will be enrolled in both phases of the study. Eligible patients will undergo
      leukapheresis in order to harvest T cells, which is the starting material for the manufacture
      of the autologous CAR-T product AUTO4 which is a TRBC1 targeting CAR T cell product.
      Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO4
      intravenously as a single dose following which they will then enter a 24-month follow-up
      period
    

Trial Arms

NameTypeDescriptionInterventions
AUTO4ExperimentalRelapsed or refractory T cell non-Hodgkin Lymphoma patients

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Male or female, aged ≥18 years.
    
              2. Willing and able to give written, informed consent to be screened for TRBC1 positive
                 T-NHL and to enter the main study.
    
              3. Confirmed diagnosis of selected T-NHL, including:
    
                   1. Peripheral T cell lymphoma NOS, or
    
                   2. Angioimmunoblastic T cell lymphoma, or
    
                   3. Anaplastic large cell lymphoma
    
              4. Confirmed TRBC1 positive tumour.
    
              5. Relapsed or refractory disease and have had ≥1 prior lines of therapy.
    
              6. Has measurable disease with ≥1 measurable lesion(s).
    
              7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
    
              8. Adequate bone marrow function without the requirement for ongoing blood products and
                 meets the following criteria:
    
                   1. Absolute neutrophil count ≥1.0 x 109/L
    
                   2. Absolute lymphocyte count ≥0.5 x 109/L (at entry and prior to leukapheresis).
    
                   3. Haemoglobin ≥80 g/L
    
                   4. Platelets ≥75 x 109/L
    
              9. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
    
                   1. Creatinine clearance (as estimated by Cockcroft Gault) ≥60 cc/min.
    
                   2. Serum alanine aminotransferase/aspartate aminotransferase ≤2.5 x upper limit of
                      normal (ULN).
    
                   3. Total bilirubin ≤25 µmol/L (1.5 mg/dL), except in patients with Gilbert's
                      syndrome.
    
                   4. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or
                      multiple gated acquisition (MUGA) cardiac scan, unless the institutional lower
                      limit of normal is lower.
    
                   5. Baseline oxygen saturation ≥92% on room air and ≤Grade 1 dyspnoea.
    
             10. For females of childbearing potential (defined as <2 years after last menstruation or
                 not surgically sterile), a negative serum or urine pregnancy test must be documented
                 at screening, prior to pre-conditioning and confirmed before receiving the first dose
                 of study treatment. For females who are not postmenopausal (<24 months of amenorrhea)
                 or who are not surgically sterile (absence of ovaries and/or uterus), a highly
                 effective method of contraception together with a barrier method must be used from the
                 start of the pre-conditioning stage and for at least 12 months after the last dose of
                 AUTO4 (study treatment). They must agree not to donate eggs (ova, oocytes) for the
                 purposes of assisted reproduction during the study and for 12 months after receiving
                 the last dose of study drug
    
             11. For males, it must be agreed that two acceptable methods of contraception are used
                 from the start of the pre-conditioning stage and for at least 12 months after the last
                 dose of AUTO4 (one by the patient - usually a barrier method, and one by the patient's
                 partner. Also, that sperm will not be donated during the treatment period and for at
                 least 12 months after the last dose of study treatment.
    
             12. No contra-indications for leukapheresis, or the pre-conditioning regimen.
    
            Exclusion Criteria:
    
            Patients meeting any of the following exclusion criteria must not be enrolled into the
            study:
    
              1. Patients with T cell leukaemia.
    
              2. Females who are pregnant or lactating.
    
              3. Prior treatment with investigational gene therapy or approved gene therapy or
                 genetically engineered cell therapy product or allogeneic stem cell transplant.
    
              4. Known history or presence of clinically relevant central nervous system (CNS)
                 pathology. Patients with a known history or prior diagnosis of optic neuritis or other
                 immunologic or inflammatory disease affecting the CNS.
    
              5. Current or history of CNS involvement by malignancy.
    
              6. Clinically significant, uncontrolled heart disease
    
                   1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial
                      fibrillation are not excluded).
    
                   2. Evidence of pericardial effusion.
    
              7. Patients with evidence of uncontrolled hypertension or with a history of hypertension
                 crisis or hypertensive encephalopathy.
    
              8. Patients with a history (within 3 months) or evidence of deep vein thrombosis or
                 pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of
                 pre-conditioning.
    
              9. Patients with active gastrointestinal (GI) bleeding.
    
             10. Patients with any major surgical intervention in the last 3 months.
    
             11. Active infectious bacterial, viral disease or fungal disease (hepatitis B virus,
                 hepatitis C virus, human immunodeficiency virus [HIV], human T cell lymphotropic virus
                 [HTLV] or syphilis) requiring treatment.
    
             12. Active autoimmune disease requiring immunosuppression.
    
             13. History of other neoplasms unless disease free for at least 2 years (adequately
                 treated carcinoma in situ, curatively treated non-melanoma skin cancer, breast or
                 prostate cancer on hormonal therapy are allowed).
    
             14. Prior treatment with programmed cell death protein 1 (PD1), programmed death ligand 1
                 (PD-L1), or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) targeted therapy, or
                 tumour necrosis factor (TNF) receptor superfamily agonists including CD134 (OX40),
                 CD27, CD137 (41BB), and CD357 (glucocorticoid induced TNF receptor family related
                 protein).
    
             15. The following medications are excluded:
    
                   1. Steroids: Therapeutic doses of corticosteroids within 72 hours of leukapheresis
                      or pre-conditioning chemotherapy administration.
    
                   2. Cytotoxic chemotherapies within 2 weeks prior to leukapheresis or AUTO4 infusion.
    
                   3. Antibody therapy use within 2 weeks prior to AUTO4 infusion, or five half-lives
                      of the respective antibody, whichever is shorter.
    
                   4. Live vaccine within 4 weeks prior to enrolment.
    
             16. Research participants receiving any other investigational agents, or concurrent
                 biological, chemotherapy, or radiation therapy.
    
             17. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to AUTO4
                 infusion.
    
             18. Patients, who in the opinion of the Investigator, may not be able to understand or
                 comply with the safety monitoring requirements of the study.
    
            For pre-conditioning chemotherapy and AUTO4 Infusion: Patients meeting any of the following
            exclusion criteria must not be treated with pre-conditioning chemotherapy or
    
            AUTO4 - and have treatment delayed until they no longer meet these criteria:
    
              1. Severe intercurrent infection at the time of pre-conditioning chemotherapy or the
                 scheduled AUTO4 infusion.
    
              2. Requirement for supplementary oxygen or active pulmonary infiltrates or significant
                 deterioration of organ function at the time of pre-conditioning chemotherapy or
                 scheduled AUTO4 infusion.
    
              3. Significant clinical deterioration of organ functions from screening, as determined by
                 the investigator.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Phase I: Safety (Frequency and severity of adverse events and serious AEs) and confirmation of Phase II dose and schedule.
    Time Frame:24 months post treatment
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Assess overall safery and tolerability in terms of frquecny and severity of all AEs and SAEs and incidence and severity of opportunistic infections following AUTO4 infusion.
    Time Frame:24 months post treatment
    Safety Issue:
    Description:
    Measure:Feasibility of generating AUTO4: Number of patients whose cells achieve successful AUTO4 manufacture as a proportion of the number of patients undergoing leukapheresis.
    Time Frame:Up to 8 weeks post leukapheresis
    Safety Issue:
    Description:
    Measure:Time to response (PR and CR)
    Time Frame:24 months post treatment
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Autolus Limited

    Trial Keywords

    • T cell lymphoma
    • Relapsed T cell Non-Hodgkin Lymphoma
    • Refractory T cell Non-Hodgkin Lymphoma
    • AUTO4

    Last Updated