A Phase I Study Investigating Safety Immunological Effects of Peripheral Blood T Lymphocytes Transduced With Anti LewisY Chimeric Receptor Gene in LewisY Positive Myeloma, Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
- Applicable to all Patients
- Patient is able to undergo apheresis of peripheral blood mononuclear cells (PBMC)
within eight weeks following registration.
- White cell count (WCC) <30/nL as higher WCC could interfere with the apheresis of
- Patient has an ECOG performance status of 0 - 1.
- Patient is deemed capable of undergoing the planned study procedures
- Patient has adequate organ function:
- bilirubin <1.5x upper limit of normal (ULN), AST/ALT ≤2.5 x ULN except in
patients with Gilbert's syndrome
- Serum Creatinine < 1.5 ×ULN or creatinine clearance > 50ml/min
- Amylase, lipase ≤1.5xULN
- Lymphocyte count of ≥0.5x109/L
- > 18 years of age.
- Patient has provided written informed consent.
- No chemotherapy or treatment with G-CSF within 4 weeks prior to the planned
- Applicable to patients with multiple myeloma
- Patient has histologically or cytologically confirmed diagnosis of multiple myeloma
plus one or more of the criteria set out below must apply:
- Presence of the following features that are known to be associated with an adverse
prognosis with conventional chemotherapy, high-dose chemotherapy and autologous stem
cell transplant (AUSCT):
- 13q deletion
- 17p deletion as p53-deletion by IHC on the bm trephine
- Translocation (4:14)
- Translocation (14:16)
- Progressive disease within 12 months after previous AUSCT
- Plasmablastic morphology
- Plasma cell leukaemia
- Patient planned for high-dose melphalan chemotherapy with AUSCT having had at
least two prior treatment regimens (which can include prior high-dose
chemotherapy and AUSCT and must include at least one of thalidomide,
lenalidomide or bortezomib).
- Patient has previously proven LewisY expression on the plasma cells prior to
study entry in an analysis as defined in study criteria
- Patient is planned to receive high dose melphalan and autograft (after apheresis
- Additional inclusion Criteria applied to patients with acute myeloid leukaemia
(AML)/high-risk myelodysplastic syndrome (MDS)
All of the following must apply:
- Patient must either have newly diagnosed AML/high-risk MDS with a poor prognosis or
relapsed/refractory AML/high-risk MDS
- Patient has previously proven LewisY expression on the myeloblasts prior to study
entry in an analysis as defined in study criteria
- Patient is planned to receive fludarabine containing regime (FCR) chemotherapy (after
apheresis of PBMC) which is planned to be the last cycle of FCR chemotherapy, no
further FCR chemotherapy should be planned within 3 months after this cycle of FCR
Definition of poor prognosis in AML/high-risk MDS
A patient with AML has a poor prognosis if any of the following is satisfied:
- Age > 65 years
- Age 56 - 65 years with any of the following single cytogenetic abnormalities: -7, -5,
trisomy 8, abnormal 3q, t(6;9), t(9;22) or t(9;11), normal karyotype with FLT3-ITD
- Age 56 - 65 years with a complex aberrant karyotype defined as >4 cytogenetic
- Any age with relapsed or refractory disease
None of the following should apply:
- Patient has had immunotherapy including corticosteroids (except Prednisolone <10mg or
equivalent) within the last 4 weeks or is planned to receive such therapy prior to
apheresis of PBMC.
- Patient has been given chemotherapy and/or G-CSF in the last 4 weeks.
- Patient has been planned to receive chemotherapy and/or growth factors of any type
before planned apheresis of PBMC
- Patient has been given experimental therapy within the last 4 weeks or is planned to
receive experimental therapy prior to apheresis of PBMC
- Patient has known clinically significant autoimmune disease with positive serology
for RHF (>20kU/L) or ANA (titre >1:40)
- Patient has a history of idiopathic pancreatitis Patient has known, biopsy proven
autoimmune inflammatory disease of the gastrointestinal tract
- Women of child bearing potential (WOCBP) who are unwilling or unable to use an
effective method of contraception to avoid pregnancy for the entire study period and
for at least 3 months after completion of study treatment.
- Women who are pregnant or breastfeeding.
- Men who are unwilling or unable to use an acceptable method of contraception for the
entire study period and for at least 3 months after completion of study treatment if
their sexual partners are WOCBP.
- Patient has known central nervous system (CNS) disease.
- Patient has a serious uncontrolled medical disorder which would impair the ability to
receive protocol therapy.