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

Primary Purpose

Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Acute Myeloid Leukaemia

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Reduced intensity haplodentical stem cell transplant
Myeloablative haploidentical stem cell transplant
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin's Lymphoma focused on measuring Haploidentical transplant, Haematological malignancy, Myeloablative, Reduced intensity

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Birmingham Heartlands
  • Bristol Royal Infirmary
  • Addenbrooke's Hospital
  • Beatson Hospital
  • St James' University Hospital
  • Royal Liverpool Hospital
  • King's College Hospital
  • St Bartholomew's Hospital
  • University College Hospital
  • Manchester Royal Infirmary
  • Freeman Hospital
  • Royal Hallamshire, Sheffield & Weston Park

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Reduced intensity haploidentical transplant

Myeloablative haploidentical stem cell transplant

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

Full Information

First Posted
May 10, 2012
Last Updated
September 27, 2021
Sponsor
University College, London
Collaborators
Bloodwise
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1. Study Identification

Unique Protocol Identification Number
NCT01597219
Brief Title
Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers
Acronym
UK-Haplo
Official Title
A UK Multicentre Study of Haploidentical Stem Cell Transplantation in Patients With Haematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 2013 (undefined)
Primary Completion Date
October 2021 (Anticipated)
Study Completion Date
October 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Bloodwise

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Haploidentical transplant, Haematological malignancy, Myeloablative, Reduced intensity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reduced intensity haploidentical transplant
Arm Type
Experimental
Arm Description
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
Arm Title
Myeloablative haploidentical stem cell transplant
Arm Type
Experimental
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Reduced intensity haplodentical stem cell transplant
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Myeloablative haploidentical stem cell transplant
Intervention Description
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
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
1 year post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Patient Inclusion Criteria Eligible for an allogeneic transplant in line with the current BSBMT indications for transplant criteria (http://bsbmt.org/indications-table/) accepted by Commissioners Age 16-70 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% Donor available aged ≥16 years 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 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 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. 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 Written informed consent Donor Inclusion Criteria Donor must be an HLA-haploidentical first degree relative of the patient. Eligible donors include biological parents, siblings, children or half-siblings Age ≥16 years Donors must meet the collection centre's usual selection criteria for related allogeneic HPC donors Patient Exclusion Criteria HLA matched, related donor able to donate Autologous haematopoietic stem cell transplant <3 months prior to enrolment Pregnancy or breastfeeding 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 Serious psychiatric or psychological disorders Absence or inability to provide informed consent Severe comorbidity (HCT-CI comorbidity score of 3 or more) or disease that prevents treatment with chemotherapy, unless otherwise agreed by the TMG Positive anti-donor HLA antibody Unable to receive 2Gy TBI (RIC pathway) or 12Gy TBI (MAC pathway) Patients with graft rejection following a previous allograft from either adult or cord blood donors Donor Exclusion Criteria Positive anti-donor HLA antibody in the recipient Pregnancy or recent birth (within 6 months prior to donating cells)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr Kavita Raj
Organizational Affiliation
King's College Hospital NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Birmingham Heartlands
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Royal Infirmary
City
Bristol
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Beatson Hospital
City
Glasgow
Country
United Kingdom
Facility Name
St James' University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Royal Liverpool Hospital
City
Liverpool
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
St Bartholomew's Hospital
City
London
Country
United Kingdom
Facility Name
University College Hospital
City
London
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle
Country
United Kingdom
Facility Name
Royal Hallamshire, Sheffield & Weston Park
City
Sheffield
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

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