The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618001090202
Ethics application status
Approved
Date submitted
20/06/2018
Date registered
29/06/2018
Date last updated
29/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Coadministration of Malignancy and Infection specific T cells after allogeneic stem cell Transplant for Acute Leukaemia with CD34+ selected stem cells
Scientific title
Coadministration of Malignancy and Infection specific T cells after allogeneic stem cell Transplant for Acute Leukaemia with CD34+ selected stem cells
Secondary ID [1] 295263 0
None
Universal Trial Number (UTN)
Trial acronym
COMITTAL34
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Acute Leukaemia 308435 0
Cytomegalovirus 308436 0
Epstein-Barr Virus 308439 0
Varicella Zoster Virus 308440 0
BK Virus 308441 0
Influenza virus 308442 0
Aspergillus 308443 0
Condition category
Condition code
Cancer 307422 307422 0 0
Leukaemia - Acute leukaemia
Infection 307423 307423 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study treatment will consist of an infusion of CD34 selected donor stem cells on day 0 of the fully-matched related allogeneic bone marrow transplant. A minimum of 21 days following the transplant, one intravenous infusion of 2 x 107/m2 of pathogen specific T cells will be given over 1 minute to all patients following myeloid engraftment. In addition, up to a total of four intravenous infusions of 2x107/m2 either WT1 specific T cells for patients with AML or CAR19 T cells for patients with ALL will be given to the patient no less than 28 days apart unless contraindicated. Such contraindications are fever, hypotension, tachycardia, hypoxemia, graft versus host disease greater than or equal to grade II in the week prior to infusion, abnormal liver function >3x upper limit normal. The pathogen specific and malignancy specific cells can be given and monitored as an outpatient (eg: the Cancer Day Suite) by study investigators or other staff as delegated by the investigator's (eg: BMT Fellow, Clinical Nurse Specialists, Nurse Practitioners). The patients will be followed up at 3 months post transplant and 6 months post transplant. ALL patients will be followed up at additional time points of 12months and yearly for 15 years for the detection of long term adverse event outcomes. The bone marrow transplant will occur and delivered as an inpatient as per standard of care.
Intervention code [1] 301599 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306394 0
Event-free survival.
Events captured will be graft failure, disease relapse or death from any cause. This information will be collected from hospital records.
Timepoint [1] 306394 0
Within 6 months post-transplant
Secondary outcome [1] 348334 0
Non-relapse mortality
If the patient dies from any other cause than relapse of their disease, being acute myeloid leukaemia (AML) acute lymphoblastic leukaemia (ALL), this will be captured as a secondary outcome. This information will be collected from hospital records.
Timepoint [1] 348334 0
Within 6 months post transplant
Secondary outcome [2] 348335 0
Relapse incidence
Recurrence of disease (AML or ALL) will be captured as a secondary outcome. Information will be collected from hospital records.
Timepoint [2] 348335 0
Within 6 months post-transplant
Secondary outcome [3] 348336 0
Graft versus host disease (GVHD) incidence and severity (composite secondary outcome)
Information will be collected from hospital records.
Timepoint [3] 348336 0
Within 6 months post-transplant
Secondary outcome [4] 348337 0
Chronic GVHD incidence and severity (composite outcomes)
Chronic GVHD will be graded using the National Institute of Health Consensus criteria. Information will be collected from hospital records.
Timepoint [4] 348337 0
Within 6 months post-transplant
Secondary outcome [5] 348338 0
Primary graft failure
Information will be collected from hospital records.
Timepoint [5] 348338 0
From transplant to 12 months post transplant
Secondary outcome [6] 348339 0
Overall survival
Information will be collected from hospital records.
Timepoint [6] 348339 0
At 6 months post-transplant
Secondary outcome [7] 348340 0
Incidence of infection
Information will be collected from hospital records and laboratory results.
Timepoint [7] 348340 0
From transplant till end of follow up (12 months for an AML patient or 15 years if an ALL patient)
Secondary outcome [8] 348341 0
Incidence of EBV related post-transplant lymphoproliferative disorder.
Information will be collected from hospital records including laboratory results.
Timepoint [8] 348341 0
From transplant till end of follow up (12 months for an AML patient or 15 years if an ALL patient)
Secondary outcome [9] 348342 0
If receiving CAR-19 Tcells: incidence of tumor lysis syndrome
Information will be collected from hospital records including laboratory results.
Timepoint [9] 348342 0
From first CAR19 infusion till end of 15 years
Secondary outcome [10] 348343 0
T cell immune reconstitution
T cell immune reconstitution is measured by CD3, CD4, CD8, CD16 and CD20 count and ELIspot in response to viral, fungal and leukaemia antigens on peripheral blood.
Timepoint [10] 348343 0
From bone marrow transplant till 12 months post transplant
Secondary outcome [11] 348604 0
Secondary graft failure
Information will be collected from hospital records.
Timepoint [11] 348604 0
From transplant to 12 months post transplant
Secondary outcome [12] 348606 0
If receiving CAR-19 Tcells:, persistence of cells
Information will be collected from hospital records including laboratory results.
Timepoint [12] 348606 0
From first CAR19 infusion till end of 15 years
Secondary outcome [13] 348607 0
If receiving CAR-19 Tcells: functional capacity of persisting cells
Information will be collected from hospital records including laboratory results.
Timepoint [13] 348607 0
From first CAR19 infusion till end of 15 years

Eligibility
Key inclusion criteria
1. Patients aged 1-69 years undergoing first myeloablative or non-myeloablative allogeneic transplantation from an HLA identical family or 10 out of 10 HLA matched (A, B, C, DRB1, DQB1) unrelated donor
2. Transplant performed for acute myeloid leukaemia or acute lymphoblastic leukemia in morphological first complete remission
3. For AML, where diagnosis or relapse samples are available, leukaemia blasts express the WT1 tumour antigen as determined by the European LeukaemiaNet standardised assay described in Candoni (et al.) 2009. WT1 overexpression will be defined by greater than 250 copies/104ABL copies in bone marrow samples or greater than 50 copies/104ABL copies in peripheral blood. For ALL, leukemia blasts express the CD19 antigen
4. Recipients of peripheral blood or bone marrow stem cells
5. Adequate hepatic and renal function (< 3 x upper limit of normal for AST, ALT, < 2 x upper limit of normal for total bilirubin, serum creatinine)
6. Estimated life expectancy of at least 6 months
7. Patient (or legal representative) has given informed consent
Minimum age
1 Years
Maximum age
69 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum anti-lymphocyte antibody) given in the 28 days immediately prior to malignancy or infection specific T cell infusion (MITI) or planned within 28 days after infusion
2. Grade II or greater graft versus host disease within 1 week prior to infusion
3. Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent) administered within 2 days prior to T cell infusion
4. Intercurrent medical, surgical or psychiatric condition which may interfere with the conduct or safety of the trial
5. Patients taking anti-viral or anti-fungal medication for CMV or proven or probable Aspergillus infection at the time of commencement of transplant conditioning
6. Previous unmanipulated donor lymphocyte infusion after transplant
7. Prior history of seizures if undergoing transplant for ALL
8. Privately insured in or outpatients (see Indemnity Issues, Section 11.4

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)
Not applicable.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Not applicable
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
20 patients will be treated on the study
A sample size of 20 patients has been chosen for the study as practical in terms of recruitment and suitable for determination of reductions in disease free survival (DFS) and estimations of other risks.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11200 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 23062 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 299852 0
Charities/Societies/Foundations
Name [1] 299852 0
Cancer Council New South Wales
Address [1] 299852 0
153 Dowling St Woolloomoolo NSW 2011
Country [1] 299852 0
Australia
Primary sponsor type
Hospital
Name
Western Sydney Local Health District, Westmead Hospital
Address
Cnr Hawkesbury and Darcy Roads
Westmead Hospital
Westmead, NSW,2145
Country
Australia
Secondary sponsor category [1] 299206 0
None
Name [1] 299206 0
None
Address [1] 299206 0
None
Country [1] 299206 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300728 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300728 0
Cnr Hawkesbury and Darcy Road
Westmead Hospital
Westmead, NSW, 2145
Ethics committee country [1] 300728 0
Australia
Date submitted for ethics approval [1] 300728 0
30/08/2016
Approval date [1] 300728 0
09/02/2017
Ethics approval number [1] 300728 0

Summary
Brief summary
The study will analyse the safety and biological efficacy of administering the investigational products (donor-derived T cells stimulated with WT1 or engineered to express a CD19 chimeric antigen receptor, together with donor derived T cells stimulated with viral and fungal antigens) for the prevention of relapse and viral/fungal illnesses in patients undergoing transplantation for acute leukaemia in first complete remission.


Who is it for?

You may be eligible for this study if you are 69 years or younger and are undergoing an allogeneic transplant for the treatment of either acute myeloid leukaemia or acute lymphoblastic leukaemia.


Study details

Participants will receive a bone marrow transplant. 21 days following the transplant, participants may receive an infusion of T cells made from their donor’s cells that is anticipated will help fight off infections. Following this, participants may be eligible to receive up to 4 Tcell infusions that is anticipated to help fight cancer.

Patients will then be followed up for 12 months (for AML patients) or 15 years (for ALL patients). Over this time you will be asked to donate extra blood for clinical trial use which will mostly be collected at blood tests that are required for normal transplant follow up.

It is hoped that this research will provide safer and more effective blood or marrow transplants for those suffering from leukaemia.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84622 0
Prof David Gottlieb
Address 84622 0
Westmead Hospital
Cnr Hawkesbury Rd and Darcy Rd
Westmead, NSW, 2145
Country 84622 0
Australia
Phone 84622 0
+61 2 8890 7417
Fax 84622 0
+61 2 9687 2331
Email 84622 0
david.gottlieb@sydney.edu.au
Contact person for public queries
Name 84623 0
Prof David Gottlieb
Address 84623 0
Westmead Hospital
Cnr Hawkesbury Rd and Darcy Rd
Westmead, NSW, 2145
Country 84623 0
Australia
Phone 84623 0
+61 2 8890 7417
Fax 84623 0
+61 2 9687 2331
Email 84623 0
david.gottlieb@sydney.edu.au
Contact person for scientific queries
Name 84624 0
Prof David Gottlieb
Address 84624 0
Westmead Hospital
Cnr Hawkesbury Rd and Darcy Rd
Westmead, NSW, 2145
Country 84624 0
Australia
Phone 84624 0
+61 2 8890 7417
Fax 84624 0
+61 2 9687 2331
Email 84624 0
david.gottlieb@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results