Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000762853
Ethics application status
Approved
Date submitted
11/04/2021
Date registered
18/06/2021
Date last updated
16/08/2024
Date data sharing statement initially provided
18/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
CAR T cell therapy for CD19-positive cancer - phase I clinical trial
Scientific title
Phase I Clinical Trial of MB.CART19.1 CD19 Chimeric Antigen Receptor (CAR)
T Cells in Relapsed or Refractory CD19-Positive Haematological Malignancy
Secondary ID [1] 303906 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B cell blood cancers, including non-Hodgkin's lymphoma and leukaemia. 321057 0
Condition category
Condition code
Cancer 318859 318859 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 318862 318862 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 318863 318863 0 0
Leukaemia - Acute leukaemia
Cancer 318864 318864 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 319965 0
Treatment: Other
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326808 0
Safety of MB.CART19.1 CAR T cells as defined by the incidence of Grade = 3 - 4 Cytokine Release Syndrome (CRS) - assessed according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for CRS.
Timepoint [1] 326808 0
6 months after the infusion of MB.CART19.1 CAR T cells
Primary outcome [2] 327560 0
Safety of MB.CART19.1 CAR T cells as defined by the incidence of Grade = 3 - 4 Immune Cell-Associated Neurotoxicity Syndrome (ICANS). ICANS will be assessed according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for ICANS.
Timepoint [2] 327560 0
6 months after the infusion of MB.CART19.1 CAR T cells
Secondary outcome [1] 392746 0
Determine the manufacturing feasibility of MB.CART19.1 CAR T cells defined as the production of MB.CART19.1 CAR T cell products that meets all release criteria and target cell dose. These will be determined from documentation at the Royal Brisbane and Women's Hospital.Cellular Therapy Laboratory, which manufactures the cells
Timepoint [1] 392746 0
Time from study enrolment to cell infusion
Secondary outcome [2] 392747 0
Incidence of cytopenia that is not resolved by Day +28 of CAR T cell infusion. Defined as CTCAE v5.0 equal to or greater than grade 3 neutropenia (where neutrophils are less than or equal to 1.0 x 10e9/L) or thrombocytopenia (where platelet count is less than or equal to 50 x 10e9/L), that is not resolved by Day+28 of CAR T cell infusion, unless due to disease.
Timepoint [2] 392747 0
28 days after the infusion of MB.CART19.1 CAR T cells
Secondary outcome [3] 393884 0
All infections CTCAE v5.0 greater than or equal to grade 2 for the first 3 calendar months and greater than or equal to grade 3 from calendar months 3 to 12 after the last MB.CART19.1.
Timepoint [3] 393884 0
From start of study intervention to 3 calendar months after MB.CART19.1 CAR T cell infusion
Secondary outcome [4] 393887 0
Cytomegalovirus reactivation, which is determined by polymerase chain reaction (PCR) - results of which are recorded in medical records.
Timepoint [4] 393887 0
For 24 months after the last MB.CART19.1 CAR T cell infusion
Secondary outcome [5] 395662 0
Invasive fungal infections, which will be assessed according to clinical, laboratory and imaging data.
Timepoint [5] 395662 0
For 24 months after the last MB.CART19.1 CAR T cell infusion
Secondary outcome [6] 395663 0
Disease response as defined by standard reporting criteria that are applicable to the specific B-cell leukaemia or lymphoma.
Timepoint [6] 395663 0
2 years after MB.CART19.1 CAR T cell infusion
Secondary outcome [7] 395664 0
Progression-free survival, which will be assessed using standard reporting criteria that are applicable for the specific B cell leukaemia or lymphoma, and can include CT scan, PET scan, and bone marrow biopsy.
Timepoint [7] 395664 0
2 years after MB.CART19.1 CAR T cell infusion
Secondary outcome [8] 395665 0
Overall survival
Timepoint [8] 395665 0
2 years after MB.CART19.1 CAR T cell infusion

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/06/2021
Actual
21/07/2021
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
30/09/2026
Actual
Sample size
Target
25
Accrual to date
23
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 18886 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 33392 0
4029 - Herston
Recruitment postcode(s) [2] 33393 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 308084 0
Government body
Name [1] 308084 0
Clinical Excellence Queensland
Country [1] 308084 0
Australia
Primary sponsor type
Government body
Name
Metro North Hospital and Health Service
Address
Level 14 Block 7
Royal Brisbane and Women's Hospital
Cnr Butterfield St and Bowen Bridge Rd
HERSTON QLD 4029
Country
Australia
Secondary sponsor category [1] 308825 0
None
Name [1] 308825 0
Address [1] 308825 0
Country [1] 308825 0
Australia
Other collaborator category [1] 281716 0
Other
Name [1] 281716 0
QIMR Berghofer Medical Research Institute
Address [1] 281716 0
300 Herston Road
Herston QLD 4006
Country [1] 281716 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308070 0
Royal Brisbane and Women's Hospital
Ethics committee address [1] 308070 0
Ethics committee country [1] 308070 0
Australia
Date submitted for ethics approval [1] 308070 0
09/11/2020
Approval date [1] 308070 0
09/12/2020
Ethics approval number [1] 308070 0
ERM #69479

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109422 0
Dr Siok Tey
Address 109422 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
Brisbane
Queensland 4029
Country 109422 0
Australia
Phone 109422 0
+61 73646 1340
Fax 109422 0
+617 3646 7371
Email 109422 0
[email protected]
Contact person for public queries
Name 109423 0
Robyn Western
Address 109423 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
Brisbane
Queensland 4029
Country 109423 0
Australia
Phone 109423 0
+61 73646 1340
Fax 109423 0
+617 3646 7371
Email 109423 0
[email protected]
Contact person for scientific queries
Name 109424 0
Siok Tey
Address 109424 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
Brisbane
Queensland 4029
Country 109424 0
Australia
Phone 109424 0
+61 73646 1340
Fax 109424 0
+617 3646 7371
Email 109424 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patient privacy


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.