Transplantation Of Umbilical Cord Blood From Unrelated Donors In Patients With Haematological Diseases Using A Myeloablative Conditioning Regimen
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- University College, London
- Enrollment
- 11
- Locations
- 12
- Primary Endpoint
- Non-relapse mortality at 100 days post transplant
Study Overview
Brief Summary
This trial is looking at using umbilical cord blood from unrelated donors after high dose chemotherapy. It is for people who have cancer of the bone marrow or lymphatic system including leukaemia and lymphoma, or a blood disorder called myelodysplastic syndrome (MDS).
The trial is for babies over 4 weeks old, children, and adults up to the age of 45.
Detailed Description
During treatment for cancers of the bone marrow or lymphatic system, a lot of the stem cells are damaged and you may need a bone marrow or stem cell transplant to replace them.
Stem cells can also be collected from the umbilical cord of newborn babies. Many people around the world have donated their baby's umbilical cords which are stored safely.
There are usually enough cells in one cord to transplant a small child, but there may not be enough cells for an older child or adult. Researchers want to see if adults and children can safely have stem cells from more than 1 umbilical cord.
Before a transplant, you have high doses of chemotherapy, sometimes with radiotherapy. This intensive conditioning aims to destroy all the cells in your bone marrow, and is called myeloablative conditioning.
The aim of this trial is to see if a transplant using cord blood cells from unrelated donors after myeloablative conditioning is safe, and whether it helps people who need a stem cell transplant but don't have a stem cell donor.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 28 Days to 45 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must be < 45 years of age and ≥ 28 days old
- •Patients with high risk, advanced or poorly responding haematological disease for which there is published evidence that haematopoietic stem cell transplantation using myeloablative conditioning is likely to be effective
- •The individual patient's disease status is such that there is no alternative therapy likely to achieve cure or provide a significant prolongation of disease-free survival
- •Left ventricular ejection fraction >45%
- •Transaminases and bilirubin < twice the upper limit of the normal range
- •Creatinine clearance > 60mls/min
- •Comorbidity index of 0 or 1
Exclusion Criteria
- •Patients with a suitably matched sibling donor or 10/10 unrelated volunteer donor available within an acceptable time period.
- •Pregnancy or breastfeeding.
- •Evidence of HIV or HTLV (I+II) infection or known HIV or HTLV positive serology
- •Current active serious infection, in particular uncontrolled fungal infection -Previous irradiation that precludes the safe administration of an additional dose of 13- 14.4 Gy of total body irradiation (TBI) in patients aged 2-45 years
- •Prior autograft
- •CML in first chronic phase responding to Imatinib or refractory blast crisis
- •Patients with acute leukaemia in morphological relapse/ persistent disease (defined as > 5% blasts in normocellular bone marrow)
- •Patients with acute myeloid leukaemia with relapse/persistent disease unresponsive to re-induction chemotherapy (defined as >20% blasts in normocellular bone marrow)
- •Malignant disease that is refractory to or progressive on salvage therapy
- •Myelofibrosis.
- •Aplastic anaemia
Arms & Interventions
Fludarabine + Cyclophosphamide + TBI
Patients aged 2-45 years (excluding AML, JMML and MDS patients aged <16 years) will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Fludarabine 25mg/m^2/day day -8 to -6 (total 75mg/m^2) Cyclophosphamide 60mg/kg day -7 and -6 (total 120mg/kg) Total body irradiation 13 - 14.4Gy in 6-8 fractions
Intervention: Umbilical Cord Blood Transplant (Other)
Fludarabine + Cyclophosphamide + TBI
Patients aged 2-45 years (excluding AML, JMML and MDS patients aged <16 years) will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Fludarabine 25mg/m^2/day day -8 to -6 (total 75mg/m^2) Cyclophosphamide 60mg/kg day -7 and -6 (total 120mg/kg) Total body irradiation 13 - 14.4Gy in 6-8 fractions
Intervention: Cyclophosphamide (Drug)
Fludarabine + Cyclophosphamide + TBI
Patients aged 2-45 years (excluding AML, JMML and MDS patients aged <16 years) will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Fludarabine 25mg/m^2/day day -8 to -6 (total 75mg/m^2) Cyclophosphamide 60mg/kg day -7 and -6 (total 120mg/kg) Total body irradiation 13 - 14.4Gy in 6-8 fractions
Intervention: Total body irradiation (Radiation)
Fludarabine + Cyclophosphamide + TBI
Patients aged 2-45 years (excluding AML, JMML and MDS patients aged <16 years) will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Fludarabine 25mg/m^2/day day -8 to -6 (total 75mg/m^2) Cyclophosphamide 60mg/kg day -7 and -6 (total 120mg/kg) Total body irradiation 13 - 14.4Gy in 6-8 fractions
Intervention: Fludarabine (Drug)
Busulfan + Cyclophosphamide + Melphalan
Patients aged < 2 years and AML, JMML and MDS patients <16 years will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Busulfan 3.2mg/kg/day in 2 or 4 doses per day, days -9 to -6 (total 12.8mg/kg). Cyclophosphamide 60mg/kg days -4 and -3 (total 120mg/kg) Melphalan 140mg/m^2 day -2
Intervention: Umbilical Cord Blood Transplant (Other)
Busulfan + Cyclophosphamide + Melphalan
Patients aged < 2 years and AML, JMML and MDS patients <16 years will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Busulfan 3.2mg/kg/day in 2 or 4 doses per day, days -9 to -6 (total 12.8mg/kg). Cyclophosphamide 60mg/kg days -4 and -3 (total 120mg/kg) Melphalan 140mg/m^2 day -2
Intervention: Cyclophosphamide (Drug)
Busulfan + Cyclophosphamide + Melphalan
Patients aged < 2 years and AML, JMML and MDS patients <16 years will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Busulfan 3.2mg/kg/day in 2 or 4 doses per day, days -9 to -6 (total 12.8mg/kg). Cyclophosphamide 60mg/kg days -4 and -3 (total 120mg/kg) Melphalan 140mg/m^2 day -2
Intervention: Busulfan (Drug)
Busulfan + Cyclophosphamide + Melphalan
Patients aged < 2 years and AML, JMML and MDS patients <16 years will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:
Busulfan 3.2mg/kg/day in 2 or 4 doses per day, days -9 to -6 (total 12.8mg/kg). Cyclophosphamide 60mg/kg days -4 and -3 (total 120mg/kg) Melphalan 140mg/m^2 day -2
Intervention: Melphalan (Drug)
Outcomes
Primary Outcomes
Non-relapse mortality at 100 days post transplant
Time Frame: 100 days post transplant
Secondary Outcomes
- Overall survival at 1 year(1 year post transplant)
- Time course of mixed chimerism established by the donor graft(28, 60, 100 days, 6 months, 1 year post transplant)
- Recovery from neutropenia and cytopenia(up to 1 year post transplant)
- Incidence of acute and chronic GVHD(100 Days and 1 year post transplant)
- Incidence of relapse(1 year post transplant)