Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

Brief Title

Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

Official Title

A UK Multicentre Study of Haploidentical Stem Cell Transplantation in Patients With Haematological Malignancies

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
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall survival


Condition

Hodgkin's Lymphoma

Intervention

Reduced intensity haplodentical stem cell transplant

Study Arms / Comparison Groups

 Reduced intensity haploidentical transplant
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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

77

Start Date

March 2013

Completion Date

October 2021

Primary Completion Date

October 2021

Eligibility 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)
      

Gender

All

Ages

16 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Dr Kavita Raj, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01597219

Organization ID

UCL/10/0411


Responsible Party

Sponsor

Study Sponsor

University College, London

Collaborators

 Bloodwise

Study Sponsor

Dr Kavita Raj, Principal Investigator, King's College Hospital NHS Trust


Verification Date

September 2021