None listed
Conditions
Brief summary
The aim of this study is to determine whether it is safe to administer a type of personalized immune cell therapy made from the white blood cells of patients with blood cancer (lymphoma and leukaemia). Who is it for? You may be eligible for this study if you are aged 18 or older and have been diagnosed with a CD19-positive B –cell blood cancer, including non-Hodgkin lymphoma or leukaemia, that has not responded to other treatments or has relapsed after previous treatments. Study Details. This study will enrol only a small number of participants as the therapy is still in the early stages of testing. All enrolled participants will undergo a comprehensive medical assessment. Participants will then have white blood cells collected over 4-6 hours via a special machine. These collected white blood cells will be used to make Chimeric Antigen Receptor (CAR) T cells which takes twelve days. Participants who are able to safely undergo chemotherapy will be given three days of intravenous chemotherapy prior to the CAR T cell infusion, which is given as an inpatient. Participants will need to stay in hospital for a few days before and after the CAR T cell infusion and attend regular follow-up visits after hospital discharge for up to 15 years. It is hoped that this research will show that this type of CAR T cell therapy is safe in patients with blood cancers. This treatment may then be used to improve access to CAR T cell therapy and improve health outcomes of future patients with similar types of blood cancer.
Interventions
Description of intervention(s) / exposure: The study intervention is MB.CART19.1 CD19 CAR T cell therapy, which is a type of gene-modified immune cell made from the participant’s blood cells. The participants will undergo a medical assessment to assess suitability for CAR T cell therapy. He or she will then undergo leukapheresis, which is a procedure where a large number white blood cells are collected through the veins. The volume collected is 240 – 300 mL. The blood cells are taken to the hos
Description of intervention(s) / exposure: The study intervention is MB.CART19.1 CD19 CAR T cell therapy, which is a type of gene-modified immune cell made from the participant’s blood cells. The participants will undergo a medical assessment to assess suitability for CAR T cell therapy. He or she will then undergo leukapheresis, which is a procedure where a large number white blood cells are collected through the veins. The volume collected is 240 – 300 mL. The blood cells are taken to the hospital laboratory to be made into MB.CART19.1 CAR T cells. Where medically safe, the participants will be given intravenous chemotherapy, consisting of fludarabine 25mg/m2/day for 3 days and cyclophosphamide 250mg/m2/day for 3 days, prior to MB.CART19.1 CAR T cell infusion. Participants who are unable to safely undergo chemotherapy can still receive MB.CART19.1 CAR T cell infusion. The MB.CART19.1 CAR T cells is in a volume of up to 150mL and is given by a specialist nurse and usually takes less than 30 minutes. Participants will need to stay in hospital for a few days before and after MB.CART19.1 CAR T cell infusion and attend regular follow-up visits after hospital discharge. This is at least once a week for 4 weeks, then monthly for 3 months, 3-monthly for 2 years after cell infusion, and then yearly for up to 15 years. Only a single dose of CAR T cell is administered but additional doses are permitted in specific settings, which include loss of CAR T cells, re-emergence of B cells, and persistent or recurrent B cell cancer, provided additional cells are available and the participants consent to additional infusion and are at least four weeks after their most recent infusion.
Sponsors
Metro North Hospital and Health Service
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(1) Age equal to or greater than 18 years old (2) Relapsed or refractory CD19-positive haematological malignancy, with prior documentation of CD19 expression by flow cytometry and/or immunohistochemistry. Re-biopsy is mandatory for relapses following treatment with blinatumomab. (3) ECOG less than or equal to 2 (4) Life expectancy equal to or greater than 12 weeks (5) Adequate cardiac function with LVEF equal to or greater than 45% (6) Adequate pulmonary reserve with pulse oximetry O2 saturation equal to or greater than 90% on room air (7) Adequate renal function: serum creatinine equal to or less than 1.5 x upper limit of normal (ULN) or eGFR or CrCl equal to or greater than 50 mL/min/1.73m2 (8) Adequate liver function: ALT and AST equal to or less than 5 x ULN unless due to malignant infiltration, and total bilirubin equal to or less than 1.5 x ULN (9) Adequate bone marrow reserve: absolute neutrophil count (ANC) equal to or greater than 1.0 x 10e9/L and platelet count equal to or greater than 50 x 10e9/L, unless secondary to malignant infiltration (10) Absolute lymphocyte count (ALC) equal to or greater than 300 /µL or absolute CD3+ T cell count equal to or greater than 150 /µL (within 30 days of signing informed consent) (11) Males and females of child-bearing potential must agree to highly effective contraception for at least 1 year after CAR T cell therapy. Women of child bearing potential must have a negative serum pregnancy test.
Exclusion criteria
(1) Participants who have undergone prior allogeneic HSCT and have active acute Graft Versus Host Disease (GVHD) equal to or greater than grade 2 or chronic GVHD requiring equal to or greater than 0.5mg/kg prednisolone or other systemic immunosuppressants (2) Participants who are HIV positive, or have active Hepatitis C (HCV) or Hepatitis B (HBV). Participants who are HBV core antibody positive, with negative HBV surface antigen and HBV DNA are eligible but require anti-viral prophylaxis. Participants who have previously cleared HCV are eligible if viral clearance has been confirmed by a hepatologist. (3) Active non-haematological malignancy, excluding adequately treated carcinoma in situ and non-melanoma skin cancer (4) Active uncontrolled bacterial, fungal or viral infections (5) Active uncontrolled neurological disorders, including uncontrolled seizure disorders (6) Uncontrolled CNS involvement due to leukaemia or lymphoma (7) Significant cardiac disease, including NYHA stage 3 or 4 congestive heart failure; myocardial infarction, unstable angina or coronary artery revascularisation within 6 months of signing informed consent; and clinically significant cardiac arrhythmia, excluding atrial fibrillation. (8) Prior treatment with other CAR T cell product or gene-modified cell product (9) Pregnancy or breast feeding. (10) Patients who are eligibile for and are able to access TGA-approved CAR T cell therapy within the clinically required timeframe
Outcome results
None listed