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: AUTO4-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/dose escalation phase and a Phase II/expansion
      phase. Patients with relapsed or refractory TRBC1 positive selected T-NHL will be enrolled in
      both phases of the study. Eligible patients will undergo leukapheresis to harvest T cells,
      the starting material for the manufacture of the autologous CAR-T product AUTO4. Following
      preconditioning 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
  • AUTO4

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. Positron emission tomography (PET)-positive measurable disease per Lugano
             classification.

          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) within 6 weeks prior to AUTO4 infusion.

         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 6 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 safety and tolerability in terms of frequency 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

October 28, 2020