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Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers (UK-Haplo)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University College, London
Sponsor:
Collaborator:
Bloodwise
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01597219
First received: May 10, 2012
Last updated: November 11, 2016
Last verified: November 2016
  Purpose
This trial investigates stem cell transplants from partially mismatched donors in patients with blood and bone marrow cancers. The trial will test two kinds of transplants - a full intensity transplant using a high dose of radiotherapy and chemotherapy, and a reduced intensity transplant with lower doses of chemotherapy and radiotherapy. Patients will be entered for the treatment pathway that is most appropriate for their level of health and fitness

Condition Intervention Phase
Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Acute Myeloid Leukaemia
Acute Lymphoblastic Leukaemia
Myelodysplastic Syndrome
Chronic Myeloid Leukaemia
Chronic Lymphocytic Leukaemia
Acquired Bone Marrow Failure Syndromes
Other Haematological Malignancies; Unrelated HSCT Indicated
Procedure: Reduced intensity haplodentical stem cell transplant
Procedure: Myeloablative haploidentical stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A UK Multicentre Study of Haploidentical Stem Cell Transplantation in Patients With Haematological Malignancies

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 78
Study Start Date: March 2013
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reduced intensity haploidentical transplant
Fludarabine 30mg/m2 IV days -6 to -2 Cyclophosphamide 14.5 mg/kg IV days -6 and -5 Total body irradiation 2Gy day -1 Stem cell transplant: day 0 Cyclophosphamide 50mg/kg days +3 & +4
Procedure: Reduced intensity haplodentical stem cell transplant
Fludarabine 30mg/m2 IV days -6 to -2 Cyclophosphamide 14.5 mg/kg IV days -6 and -5 Total body irradiation 2Gy day -1 Stem cell transplant: day 0 Cyclophosphamide 50mg/kg days +3 & +4
Experimental: Myeloablative haploidentical stem cell transplant
Total body irradiation 12Gy in 8 fractions days -9 to -6 Donor lymphocyte infusion day -6 Cyclophosphamide 60mg/kg IV days -3 & -2 Stem cell transplant day 0
Procedure: Myeloablative haploidentical stem cell transplant
Total body irradiation 12Gy in 8 fractions days -9 to -6 Donor lymphocyte infusion day -6 Cyclophosphamide 60mg/kg IV days -3 & -2 Stem cell transplant day 0

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Patient Inclusion Criteria

  1. Eligible for an allogeneic transplant in line with the current BSBMT indications for transplant criteria (http://bsbmt.org/indications-table/) accepted by Commissioners
  2. Age 16-70
  3. Adequate physical function

    • Cardiac: LVEF at rest ≥45%, or shortening fraction ≥25%
    • Hepatic: Bilirubin ≤35mmol/l; AST/ALT and alkaline phosphatase <5 x ULN
    • Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, creatinine clearance or GFR >40ml/min/1.73m2
    • Pulmonary: FEV1, FVC, DLCO (diffusion capacity) >50% predicted (corrected for haemoglobin); if clinically unable to perform pulmonary function tests then O2 saturation >92% on room air
    • Performance status: Karnofsky score ≥60%
  4. Donor available aged ≥16 years
  5. Needs an urgent transplant where a 10/10 HLA matched sibling or unrelated donor is unavailable in a timely manner. An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant centre or low likelihood of finding a matched unrelated donor
  6. HLA typing will be performed at high resolution (allelic) for the HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 loci. A minimum match of 5/10 is required
  7. The donor and recipient must be identical as determined by high resolution typing at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1. Fulfilment of this criterion is sufficient evidence that the donor and recipient share one HLA haplotype and typing of additional family members is not required.
  8. Patient must have received cytotoxic chemotherapy within 3 months of the consent date (measured from the start date of the most recent cycle of chemotherapy) except patients with aplastic anaemia, unless otherwise agreed by the TMG (see section 5.3.4). The use of monoclonal antibody therapy may be considered cytotoxic chemotherapy, but must be agreed by the TMG
  9. Written informed consent

Donor Inclusion Criteria

  1. Donor must be an HLA-haploidentical first degree relative of the patient. Eligible donors include biological parents, siblings, children or half-siblings
  2. Age ≥16 years
  3. Donors must meet the collection centre's usual selection criteria for related allogeneic HPC donors

Patient Exclusion Criteria

  1. HLA matched, related donor able to donate
  2. Autologous haematopoietic stem cell transplant <3 months prior to enrolment
  3. Pregnancy or breastfeeding
  4. Uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiological findings), the inclusion of patients with an uncontrolled viral or fungal infection can be agreed by the TMG
  5. Serious psychiatric or psychological disorders
  6. Absence or inability to provide informed consent
  7. Severe comorbidity (HCT-CI comorbidity score of 3 or more) or disease that prevents treatment with chemotherapy, unless otherwise agreed by the TMG
  8. Positive anti-donor HLA antibody
  9. Unable to receive 2Gy TBI (RIC pathway) or 12Gy TBI (MAC pathway)
  10. Patients with graft rejection following a previous allograft from either adult or cord blood donors

Donor Exclusion Criteria

  1. Positive anti-donor HLA antibody in the recipient
  2. Pregnancy or recent birth (within 6 months prior to donating cells)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597219

Contacts
Contact: Ellice Marwood +44(0)207 679 9860 ctc.uk-haplo@ucl.ac.uk

Locations
United Kingdom
Birmingham Heartlands Recruiting
Birmingham, United Kingdom
Contact: Dr Shankara Paneesha         
Bristol Royal Infirmary Recruiting
Bristol, United Kingdom
Principal Investigator: Dr Rachel Protheroe         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Principal Investigator: Dr Ben Uttenthal         
Beatson Hospital Recruiting
Glasgow, United Kingdom
Principal Investigator: Dr Dave Irvine         
St James' University Hospital Recruiting
Leeds, United Kingdom
Principal Investigator: Dr Maria Gilleece         
Royal Liverpool Hospital Recruiting
Liverpool, United Kingdom
Principal Investigator: Dr Rahuman Salim         
King's College Hospital Recruiting
London, United Kingdom
Principal Investigator: Dr Kavita Raj         
St Bartholomew's Hospital Recruiting
London, United Kingdom
Principal Investigator: Dr Matthew Smith         
University College Hospital Recruiting
London, United Kingdom
Principal Investigator: Prof Stephen Mackinnon         
Manchester Royal Infirmary Recruiting
Manchester, United Kingdom
Principal Investigator: Dr Eleni Tholouli         
Freeman Hospital Recruiting
Newcastle, United Kingdom
Principal Investigator: Prof Matthew Colin         
Royal Hallamshire, Sheffield & Weston Park Recruiting
Sheffield, United Kingdom
Principal Investigator: Prof John Snowden         
Sponsors and Collaborators
University College, London
Bloodwise
Investigators
Principal Investigator: Dr Kavita Raj King's College Hospital NHS Trust
  More Information

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01597219     History of Changes
Other Study ID Numbers: UCL/10/0411 
Study First Received: May 10, 2012
Last Updated: November 11, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University College, London:
Haploidentical transplant
Haematological malignancy
Myeloablative
Reduced intensity

Additional relevant MeSH terms:
Lymphoma
Leukemia
Syndrome
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Pancytopenia
Hemoglobinuria, Paroxysmal
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, B-Cell
Myeloproliferative Disorders
Anemia, Hemolytic

ClinicalTrials.gov processed this record on December 02, 2016