Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

Study Overview
=================
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

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

Conditions
-----------------
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

Intervention / Treatment
-----------------
* Procedure: Reduced intensity haplodentical stem cell transplant
* Procedure: Myeloablative haploidentical stem cell transplant


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced intensity haploidentical transplant<br>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<br>* 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<br>|
| Experimental: Myeloablative haploidentical stem cell transplant<br>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<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 1 year post transplant | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Haploidentical transplant, Haematological malignancy, Myeloablative, Reduced intensity