Pilot Study of Unrelated Cord Blood Transplantation

Phase 2

Terminated

• Conditions: Leukemia, Myeloid, Acute; Leukemia, Lymphoblastic, Acute; Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Hodgkin Disease
• Interventions: Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Melphalan; Radiation: Radiotherapy; Drug: Intravenous busulphan; Drug: Thymoglobulin; Drug: Ciclosporin; Drug: Mycophenolate mofetil (MMF)

• Registration Number: NCT00916045
• Lead Sponsor: King's College Hospital NHS Trust

Brief Summary

The purpose of this study is to determine the safety and feasibility of unrelated double and single cord blood transplantation in patients with haematological malignancies using reduced-intensity or myeloablative conditioning regimens.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-06-05
• Study First Submitted QC: 2009-06-05
• Study First Posted: 2009-06-08
• Study Start: 2009-09
• Status Verified: 2012-03
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Last Update Submitted: 2015-02-10
• Last Update Posted: 2015-02-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

reduced-intensity conditioning regimen (For both FluMel & FluCyTBI regimens):

1. Patients with an available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor or 10/10 unrelated bone marrow donor
2. ECOG performance status worse than 2
3. Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%.
4. Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST > 5 times upper limit of normal.
5. Severe hypoxaemia, pO2 < 70 mm Hg, with decreased DLCO < 50% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 50% of predicted.
6. Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
7. Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI).
8. Patients who have received previous treatment with Thymoglobulin®
9. HIV or HTLV positive patients.
10. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
11. Life expectancy severely limited by diseases other than the disease indication for transplant
12. Serious concurrent uncontrolled infection e.g. active tuberculosis, mycoses or viral infection
13. Serious psychiatric/ psychological disorders
14. Absence of /inability to provide informed consent
15. Within 6 months of prior myeloablative transplant.
16. Patients with acute leukaemia in morphological relapse/ persistent/ progressive disease
17. Intermediate or high grade NHL, mantle cell NHL and Hodgkin's disease that is refractory or progressive on salvage therapy.
18. Myelofibrosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Myeloblative conditioning regimen	Thiotepa	-
Myeloblative conditioning regimen	Thymoglobulin	-
Reduced intensity conditioning regimen - FluCyTBI	Cyclophosphamide	-
Reduced intensity conditioning regimen - FluCyTBI	Thymoglobulin	-
Reduced intensity conditioning regimen - FluCyTBI	Ciclosporin	-
Reduced intensity conditioning regimen - FluMel	Fludarabine	-
Reduced intensity conditioning regimen - FluMel	Melphalan	-
Reduced intensity conditioning regimen - FluMel	Ciclosporin	-
Reduced intensity conditioning regimen - FluCyTBI	Radiotherapy	-
Reduced intensity conditioning regimen - FluMel	Mycophenolate mofetil (MMF)	-
Myeloblative conditioning regimen	Intravenous busulphan	-
Myeloblative conditioning regimen	Ciclosporin	-
Myeloblative conditioning regimen	Mycophenolate mofetil (MMF)	-
Reduced intensity conditioning regimen - FluCyTBI	Mycophenolate mofetil (MMF)	-
Myeloblative conditioning regimen	Fludarabine	-
Reduced intensity conditioning regimen - FluCyTBI	Fludarabine	-
Reduced intensity conditioning regimen - FluMel	Thymoglobulin	-

Primary Outcome Measures

Name	Time	Method
Treatment related mortality at day 100	Day 100

Secondary Outcome Measures

Name	Time	Method
Quality of life	Pre-transplant and months 6, 12, 18 and 24
Incidence of grade II-IV and III-IV acute GVHD	Days 28, 56, 100 and months 6, 9, 12, 18 and 24
One year overall survival for each treatment cohort	1 year
Incidence of CMV, adenovirus and EBV activation	Twice a week pre-transplant to day 100 then weekly or as clinically indicated
Immune reconstitution	Days 14, 28, 56, 100 and months 6, 9, 12, 18 and 24
Dynamics of EBV infection and immunity following cord blood transplantation	Days 14, 28, 56, 100 and months 6, 9 and 12
The development (if any) of transplant associated post transplant lymphoproliferative disease (PTLD)	Days 14, 28, 56, 100 and months 6, 9 and 12
Incidence of one year relapse or disease progression for each treatment cohort	1 year
Chimerism	Days 14 (myeloblative conditioning only), 28, 56, 100 and months 6 and 12
Incidence of chronic GVHD during the first year	Day 100 and months 6 and 12
Incidence of platelet engraftment by 6 months	Days 14, 28, 56, 100 and month 6
Disease free survival at one year post-transplant for each cohort	1 year
Incidence of neutrophil engraftment by day 42	Days 14, 28 and 42
Incidence of systemic infections	Twice a week pre-transplant to day 100 then weekly or as clinically indicated
Identify any possible predictive markers for patients most at risk of PTLD development	Days 14, 28, 56, 100 and months 6, 9 and 12

Trial Locations

Locations (1)

King's College Hosptial NHS Foundation Trust; 🇬🇧 London, United Kingdom