Coadministration of Malignancy and Infection specific T cells after allogeneic stem cell Transplant for Acute Leukaemia with CD34+ selected stem cells
Western Sydney Local Health District, Westmead Hospital
20 participants
Oct 12, 2018
Interventional
Conditions
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.
Eligibility
Inclusion Criteria7
- 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
- Transplant performed for acute myeloid leukaemia or acute lymphoblastic leukemia in morphological first complete remission
- 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
- Recipients of peripheral blood or bone marrow stem cells
- 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)
- Estimated life expectancy of at least 6 months
- Patient (or legal representative) has given informed consent
Exclusion Criteria8
- 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
- Grade II or greater graft versus host disease within 1 week prior to infusion
- Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent) administered within 2 days prior to T cell infusion
- Intercurrent medical, surgical or psychiatric condition which may interfere with the conduct or safety of the trial
- Patients taking anti-viral or anti-fungal medication for CMV or proven or probable Aspergillus infection at the time of commencement of transplant conditioning
- Previous unmanipulated donor lymphocyte infusion after transplant
- Prior history of seizures if undergoing transplant for ALL
- Privately insured in or outpatients (see Indemnity Issues, Section 11.4
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Interventions
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.
Locations(1)
View Full Details on ANZCTR
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ACTRN12618001090202