Phase I/II study evaluating AUTO4 (an experimental drug derived from the patient's own blood) in patients with T Cell Lymphoma (a type of blood cancer)
- Conditions
- Relapsed or refractory T cell Non-Hodgkin Lymphoma (T-NHL)MedDRA version: 20.0 Level: HLGT Classification code 10025321 Term: Lymphomas non-Hodgkin's T-cell System Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001965-26-GB
- Lead Sponsor
- Autolus Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 200
1. Male or female, aged =18 years.
2. Willing and able to give written, informed consent to the study.
3. Confirmed diagnosis of selected T-NHL including:
a. Peripheral T cell lymphoma, not otherwise specified (NOS), or
b. Angioimmunoblastic T cell lymphoma or
c. Anaplastic large cell lymphoma.
4. Confirmed TRBC1 positive tumour.
5. Relapse 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 or and meets the following criteria:
a. Absolute Neutrophil Count =1.0 x 10e9/L
b. Absolute lymphocyte count =0.5 x 10e9/L (at entry and prior to leukapheresis)
c. Haemaglobin =80g/L
d. Platelets =75 x 10e9/L
9. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
a. Creatinine clearance (as estimated by Cockcroft Gault) =60 cc/min.
b. Serum alanine aminotransferase / aspartate aminotransferase =2.5 x upper limit of normal ULN.
c. Total bilirubin =25 µmol/L (1.5 mg/dL), except in subjects with Gilbert’s syndrome.
d. 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
e. 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 preconditioning and confirmed before receiving the first dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Patients with T cell leukaemia.
2. Females who are pregnant or lactating.
3. Prior treatment with investigational 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, such as epilepsy, paresis, aphasia, stroke within the prior 3 months, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis. 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 (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick-sinus syndrome, or electrocardiographic evidence of acute ischaemia or Grade 3 conduction system abnormalities unless the patient has a pacemaker) or a recent (within 12 months) cardiac event.
a. Uncontrolled cardiac arrhythmia (rate-controlled atrial fibrillation are not excluded).
b. 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 recent history 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 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:
a. Steroids: Therapeutic doses of corticosteroids within 72 hours of leukapheresis or pre-conditioning chemotherapy administration. However, physiological replacement, topical, and inhaled steroids are permitted.
b. Cytotoxic chemotherapies within 2 weeks prior to leukapheresis or AUTO4 infusion.
c. Antibody therapy use within 2 weeks prior to AUTO4 infusion, or five half-lives of the respective antibody, whichever is shorter.
d. Live vaccine within 4 weeks prior to enrolment.
16. Research participants receiving any other investigational agents, or concurrent b
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method