E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukaemia Myelodysplastic syndromes Therapy related AML or MDS Philadelphia positive Chronic Myeloid Leukaemia Acute lymphoblastic leukaemia Non-Hodgkin's lymphoma (follicular lymphoma, mantle cell lymphoma, high grade non-Hodgkin's lymphoma, adult T-cell leukaemia/lymphoma, peripheral T-cell lymphoma) Hodgkin's lymphoma Chronic lymphoblastic leukaemia Acquired bone marrow failure syndromes Other haematological malignancies for which an unrelated BMT is indicated |
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E.1.1.1 | Medical condition in easily understood language |
This trial investigates transplants for a wide variety of cancers affecting the blood, bone marrow and lymphatic system. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066355 |
E.1.2 | Term | Treatment related acute myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009013 |
E.1.2 | Term | Chronic myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067070 |
E.1.2 | Term | Follicular B-cell non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061275 |
E.1.2 | Term | Mantle cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003622 |
E.1.2 | Term | ATLL |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034624 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether it is possible to carry out haploidentical/HLA mismatched donor peripheral blood stem cell transplants using high dose cyclophosphamide safely and effectively |
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E.2.2 | Secondary objectives of the trial |
To study the following: - How long haploidentical transplants control patients' disease for - How long patients survive after haploidentical transplants - Rates of infection after haploidentical transplants - Rates of graft-versus-host disease after haploidentical transplants - The quality of life of recipients undergoing these transplants - The health economics of doing haploidentical transplants |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In general this encompasses all haematological disorders where a volunteer unrelated transplant is clinically indicated and the patient is in complete remission (CR) for leukaemia or chemosensitive partial remission (PR) or CR for lymphoma. The patient should be eligible for an allogeneic transplant in line with the current BSBMT indications for transplant criteria (http://bsbmt.org/indications-table/) accepted by Commissioners.
• Acute Myeloid Leukaemia • Myelodysplastic syndromes • Philadelphia +ve chronic myeloid leukaemia • Acute lymphoblastic leukaemia • Non-Hodgkin’s lymphoma • Hodgkin’s disease • Chronic lymphocytic leukaemia • Acquired bone marrow failure syndromes • Other haematological malignancies for which an unrelated bone marrow transplant is indicated
Patient Inclusion Criteria – Recipient 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. 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 |
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E.4 | Principal exclusion criteria |
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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival at 1 year post transplant |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Overall survival at 2 years post transplant - Progression-free survival at 1 and 2 years post transplant - Neutrophil and platelet engraftment - Graft failure - Incidence of acute and chronic GVHD - Incidence of infection, including CMV, adenovirus and EBV - Non-relapse mortality - Time to relapse/progression - Quality of life/health economics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: 2 years post transplant PFS: 1 year and 2 years post transplant ENGRAFTMENT: 28 and 100 days post transplant GRAFT FAILURE: Ongoing from 28 days until 1 year post transplant INFECTION: Ongoing during the first 2 years post transplant, with particular interest in viral reactivation during the first 6 monts post transplant NON-RELAPSE MORTALITY: 100 days, 6 months and 1 year post transplant GVHD: Ongoing during the first 2 years post transplant TIME TO PROGRESSION: 1 and 2 years post transplant HEALTH ECONOMICS: Ongoing during the first 2 years post transplant QoL: Pre-transplant, 3 months, 1 & 2 years post transplant
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 30 |