1. RIC UCBT
Transplantation of Umbilical Cord Blood from Unrelated Donors in Patients with Haematological Diseases using a Reduced Intensity Conditioning Regimen
Phase II trial involving 60 patients with haematological disease, designed to assess the safety and efficacy of of unrelated umbilical cord blood transplantation using a non-myeloablative conditioning regiment in a multi-institution UK setting
SECONDARY OBJECTIVES
Mixed Chimerism
Haematopoietic recovery
Cumulative incidence of acute GVHD (Up to day 100)
Cumulative Incidence of chronic GVHD (Up to 1 year)
Incidence of Relapse
Overall survival at 1 year
PATIENT ELIGIBILITY
High risk, advanced or poorly responding haematological disease for which haematopoietic stem cell transplantation is likely to be effective.
No available 5-6/6 HLA-A, -B, DRB1 matched sibling donor or 10/10 unrelated volunteer donor available within an acceptable time period
Disease status such that there is no alternative therapy likely to achieve cure or provide a significant prolongation of disease-free survival
Age 2-60 years (Patients aged years must have a co-morbidity index of 0-1 unless agreed by the TMG)
Karnofsky score >60% (Adults) or a Lansky score 50% (Paeds)
Written informed consent of patient or parent/legal representative (if under the age of 16)
Prior autograft or exposure to combination chemotherapy in the six months preceding UCB transplant
Current transplant at least 6 months after any prior myeloablative transplant
Adequate renal, hepatic, cardiac & pulmonary function
No pregnant or lactating women
No CML, acute leukaemia in morphological relapse/persistent disease, myelofibrosis, acquired aplastic anaemia, congenital immune deficiency, congenital immune deficiencies or malignant disease that is refractory to or progressive on salvage therapy
HIV negative
No previous radiotherapy that would preclude the administration of an additional 200 cGy of total body irradiation
STUDY DESIGN
UCB graft selection
Unit selection is based on cryopreserved total nucleated cell (TNC) dose and HLA-A, -B and -DRB1 match
All units must be >4/6 matched to the recipient. If two units are to be infused they must also be >4/6 matched to each other
If multiple units are available for a given degree of HLA match, the largest will be chosen
CD34 cell dose will not be used in unit selection unless 2 units of equal HLA match are within 0.3x107 TNC/kg of each other and are available from the same bank. In this instance, the unit with the larger CD34+ cell dose will be used
Eligible patients with suitable cord blood unit
Follow up (2 years)
Registration
RIC UCBT
(Cyclophosphamide, Fludarabine & 200cGy TBI conditioning)
Consent & pre-registration investigations
BIOLOGICAL SAMPLES
There is no central pathology review for this trial
Bone marrow aspirate and trephine will be taken at baseline and 21 days. Further samples will also be taken at 28 days if required to assess slow engraftment
Chimerism analysis on peripheral blood samples will be performed at serial time-points throughout
SAMPLE SIZE: 60 patients
RIC UCBT – Haematology Trials Group Cancer Research UK & UCL Cancer Trials Centre 90 Tottenham Court Road, London, W1T 4TJ
CHIEF INVESTIGATOR:
Dr Rachael Hough – University College London
PRIMARY OBJECTIVES
Non-relapse mortality 100 days post-transplant