Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

NCT01597219 | Completed Phase 2 DMC

• 1 other identifier: UCL/10/0411
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 12

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

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

Keywords

Haploidentical transplant; Haematological malignancy; Myeloablative; Reduced intensity

Outcome Measures

Primary Outcomes (1)

• Overall survival

  1 year post transplant

Study Arms (2)

Reduced intensity haploidentical transplant

EXPERIMENTAL

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

Myeloablative haploidentical stem cell transplant

EXPERIMENTAL

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

Interventions

Reduced intensity haplodentical stem cell transplant PROCEDURE

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

Reduced intensity haploidentical transplant

Myeloablative haploidentical stem cell transplant PROCEDURE

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

Myeloablative haploidentical stem cell transplant

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 must be an HLA-haploidentical first degree relative of the patient. Eligible donors include biological parents, siblings, children or half-siblings

You may not qualify if:

• HLA matched, related donor able to donate
• Autologous haematopoietic stem cell transplant \<3 months prior to enrolment
• Pregnancy or breastfeeding
• 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
• Positive anti-donor HLA antibody in the recipient
• Pregnancy or recent birth (within 6 months prior to donating cells)

Sponsors & Collaborators

• University College, London: lead
• Bloodwise: collaborator

Study Sites (12)

Birmingham Heartlands

Birmingham, United Kingdom

Location

Bristol Royal Infirmary

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Beatson Hospital

Glasgow, United Kingdom

Location

St James' University Hospital

Leeds, United Kingdom

Location

Royal Liverpool Hospital

Liverpool, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

University College Hospital

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Royal Hallamshire, Sheffield & Weston Park

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, B-Cell; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Leukemia, Lymphoid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

Study Officials

• Dr Kavita Raj

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 11, 2012
• Study Start: March 1, 2013
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: May 3, 2024

Record last verified: 2024-05

Locations

GB (12)