A Phase I/II study to evaluate AUTO3 in adults withDiffuse Large B Cell Lymphoma who have previously received approved treatment(s) and subsequently progressed.
- Conditions
- Relapsed or refractory Diffuse Large B Cell Lymphoma (DLBCL) and large B cell lymphoma subsetsMedDRA version: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10036711Term: Primary mediastinal large B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 21.0Level: PTClassification code 10036710Term: Primary mediastinal large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004682-11-GB
- Lead Sponsor
- Autolus Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 171
1. Male or female, aged =18 years that provide written informed consent.
2. Eastern Cooperative Oncology Group performance status 0 to 1.
3. Histologically confirmed DLBCL and large B cell lymphoma (at last relapse) and permitted subsets.
4. Chemotherapy-refractory disease or Relapse after at least two lines of therapy or after ASCT.
5. PET-positive disease per Lugano classification.
6. Females of childbearing potential must have a negative serum or urine pregnancy test at screening, prior to pre-conditioning and confirmed before receiving the first dose of AUTO3.
7. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
a. Creatinine clearance =40 cc/min
b. Serum alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) =2.5 x ULN.
c. Total bilirubin =1.5 x ULN.
d. Left Ventricular Ejection Fraction (LVEF) =50% unless the institutional lower limit of normal is lower.
e. Baseline oxygen saturation >92% on room air and =Grade 1 dyspnoea.
8. Patient has adequate bone marrow function and meets the following criteria:
a. Absolute neutrophil count =1.0 x 10e9/L.
b. Absolute lymphocyte count =0.3 x 10e9/L (at enrolment and prior to leukapheresis).
c. Haemoglobin =80 g/L;
d. Platelets =75 x 10e9/L.
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 101
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
1. Prior allogeneic haematopoietic stem cell transplantation.
2. Females who are pregnant or lactating.
3. History or presence of clinically relevant central nervous system (CNS) pathology within 3 months prior to enrolment.
4. Patients with active CNS involvement by malignancy.
5. Clinically significant, uncontrolled heart disease or a recent cardiac event.
6. Active bacterial, viral disease or fungal infection requiring systemic treatment.
7. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents in the last 2 years.
8. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, idiopathic pneumonitis.
9. Prior treatment with therapy targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated protein 4 (CTLA 4) or prior treatment with tumour necrosis factor receptor superfamily (TNFRSF) agonists and CD357 (glucocorticoid-induced tumour necrosis factor receptor family related protein) within 6 weeks prior to AUTO3 infusion.
10. Prior CD19 or CD22 targeted therapy.
11. The following medications are excluded:
a. Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to AUTO3 administration.
b. Immunosuppression: Immunosuppressive medication must be stopped =2 weeks prior to leukapheresis or AUTO3 infusion.
c. Cytotoxic chemotherapies within 2 weeks of infusion and 1 week prior to leukapheresis.
d. Antibody therapy use including anti-CD20 therapy within 4 weeks prior to infusion, or 5 half-lives of the respected antibody, whichever is shorter.
e. Granulocyte-colony stimulating factor (G-CSF) less than 10 days prior to leukapheresis.
f. Live vaccine =4 weeks prior to enrolment.
g. Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy within 2 weeks prior to starting pre-conditioning
chemotherapy.
12. Prior radiation therapy within 4 weeks or chest within 24 weeks of AUTO3 infusion .
13. Patients receiving any other investigational agents or concurrent biological, chemotherapy or radiation therapy.
14. Known allergy to albumin, dimethyl sulphoxide, cyclophosphamide or fludarabine, anti-PD-1 antibody or tocilizumab.
15. Contraindications to receive anti-PD1 antibody will be excluded from cohorts requiring administration this administration.
Phase I expansion only:
16. Subjects who do not have adequate caregiver support for outpatient care.
17. Subjects who are staying greater than 60 minutes (or whatever is permissible per institutional outpatient transplant SOP)?from the clinical trial site at the time of treatment.
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