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Cytarabine

Fludarabine

Fludarabine phosphate

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Antineoplastic Agents, Alkylating

First Randomisation (closed to recruitment) - control arm: Intermediate dose Cytarabine (1g/m\^2 administered by intravenous infusion over 2 hours on days 1-5 inclusive)

First Randomisation (closed to recruitment) - experimental arm: Vyxeos (29mg/65mg/m\^2 administered by intravenous infusion over 90 minutes on days 1 and 3)

Second Randomisation - under 55 years - control arm: Fludarabine (40mg/m\^2 days -7, -6, -5, and -4), Busulphan (3.2mg/kg days -7, -6, -5 and -4)

Second Randomisation - under 55 years - experimental arm: Thiotepa (5mg/kg day -7 and -6), Busulphan (3.2mg/kg days -5, -4 and -3), Fludarabine (50mg/m\^2 days -5, -4 and -3)

Third Randomisation - 55 years and over (or under 55 with comorbidities) - control arm: Fludarabine (30mg/m\^2 days -6, -5, -4, -3 and -2), Busulphan (3.2mg/kg days -6 and -5)

Third Randomisation - 55 years and over (or under 55 with comorbidities) - experimental arm: Thiotepa (5mg/kg day -6), Busulphan (3.2mg/kg days -5 and -4), Fludarabine (50mg/m\^2 days -5, -4, and -3)

Vyxeos administered by intravenous infusion

Vyxeos

Fludarabine administered by intravenous infusion

Busulphan administered by intravenous infusion

Busulphan

Thiotepa administered by intravenous infusion

Cytarabine administered by intravenous infusion

Charles Craddock, Professor

Treatment options for older adults with Acute Myeloid Leukaemia (AML) and Myelodysplasia (MDS) are limited. Although stem cell transplantation remains one of the most effective treatments it is associated with severe side effects which have until recently prevented its use in older adults. In the last decade the use of reduced intensity transplants has allowed the extension of the potentially curative effect of transplantation to older patients in whom it was previously precluded. Although a major advance such transplants are associated with a high risk of disease relapse particularly in patients with high risk disease.

This study will evaluate new transplant strategies with the aim of improving the outcome of patients with AML and high risk MDS after stem cell transplantation. Three approaches to improve transplant outcome will be studied:

1. Comparing the new pre-transplant consolidation therapy vyxeos with the standard consolidation therapy (Randomisation 1 is now closed to recruitment).
2. Comparing new conditioning therapies in patients under the age of 55 years
3. Comparing new conditioning therapies in patients aged 55 and over

All patients will be followed up for a minimum of 2 years.

This is a randomised, international, phase II/III, multicentre, clinical trial in patients with AML and MDS undergoing allo-SCT. Patients with AML or MDS who fulfil the eligibility criteria will be invited to participate in the trial across centers performing allo-SCT.

Patients will be randomised to treatment based on a minimisation algorithm prepared at the Cancer Research UK Clinical Trials Unit (CRCTU).

Randomisation 1 (R1) (closed to recruitment) will compare the novel consolidation therapy vyxeos with the standard consolidation therapy intermediate dose cytarabine.

Randomisation 2 (R2) will compare the novel conditioning regimen thiotepa/busulphan/fludarabine (TBF) with the standard conditioning therapy fludarabine/busulphan (FB4) in patients aged under 55 years of age.

Randomisation 3 (R3) will compare the novel conditioning regimen mini thiotepa/busulphan/fludarabine (mini TBF) with the standard regimen fludarabine/busulphan (FB2) in patients aged 55 years of age and over (or patients aged under 55 with comorbidities).

A Trial of Treatments to Assess the Effects on Outcome of Adults With AML and MDS Undergoing Allogeneic SCT

An International Randomised Clinical Trial of Therapeutic Interventions to Assess the Effects on Outcome in Adults With Acute Myeloid Leukaemia and High Risk Myelodysplasia Undergoing Allogeneic Stem Cell Transplantation.

Defined as time from entering the relevant randomisation to the relevant question until death from any cause. Patients who are alive at the end of the trial or have been lost to follow up will be censored at their date last seen. For randomisations 2 and 3 this outcome will also be calculated as time from transplantation in order to run a sensitivity analysis.

Change in minimal residual disease status. A patient will be categorised as either MRD status reduction (MRD positive to negative), MRD remain negative, MRD remain positive or MRD progression (MRD negative to positive) - Randomisation 1 only

DFS defined as time from randomisation to the relevant question to the first of relapse or death from any cause. Patients who are alive and disease free at the end of the trial will be censored at their date known to be alive.

CIR defined as time from randomisation to the relevant question to the date of relapse. Patients who die prior to relapse will be treated as a competing risk and patients who are alive and relapse free at the end of the trial will be censored at their date last seen.

NRM defined as the time from randomisation to the relevant question to date of non-relapse death. Patients who die post-relapse will be treated as a competing risk and patients who are alive at the end of the trial will be censored at their date last seen.

The EORTC QLQ-C30 uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4 ("Not at all" to "Very much"). For the raw score, less points are considered to have a better outcome. For the questions 29 and 30 it uses a 7-points scale. The scale scores from 1 to 7 ("very poor" to "excellent"). More points are considered to have a better outcome.

EQ5D is one of the most widely used health states descriptive system. EQ-5D questionnaires have 5 dimensions: "Mobility", "Human Autonomy," "Current Activities", "Pain / Discomfort", "Anxiety / Depression" and all dimensions are described by 3 problem levels corresponding to patient response choices. A quality of life score is obtained according to the answers to the questionnaires.

Incidence of acute and chronic GvHD of any grade - Randomisation 2 and 3 only

Defined as loss of donor cells after transplantation - Randomisation 2 and 3 only

Defined as the number of patients who report one or more adverse event of grade 3 or higher or a serious adverse event of any grade

Jazz Pharmaceuticals

IMPACT (funded by NHS Blood & Transplant, Anthony Nolan and Leukaemia UK)

Adienne SA

University of Birmingham

Precancerous Conditions

Thymoglobulin

Antilymphocyte Serum

Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline

Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.

Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.

Thymoglobuline will be given intravenously over a minimum of 6 hours for the first two doses and 4 hours for the subsequent doses. Acute side effects of ATG appear to be reduced if a very low dose is given for the first injection. Thymoglobuline 0.5mg/kg iv on day -4, 1.5mg/kg/day on day -3; and 2mg/kg/day iv on day -2 to -1 inclusive.

Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme

The source of stem cells will be PBSC wherever possible. Patients whose donors decline or are unable to donate PBSC will be transplanted with marrow cells.

Haematopoietic stem cell infusion

Ghulam J Mufti, MB, DM, FRCP, FRCPath

The purpose of this study is to determine the safety and feasibility of conditioning with fludarabine, busulphan and thymoglobuline in patients with myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative disorders (MDS/MPD) or acute myeloid leukaemia (AML) undergoing haematopoietic stem cell allograft with granulocyte colony-stimulating factor (G-CSF)-mobilised peripheral blood stem cells (PBSC) (or bone marrow) from HLA compatible sibling donors.

Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin

Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome and Acute Myeloid Leukaemia Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial of Treatments to Assess the Effects on Outcome of Adults With AML and MDS Undergoing Allogeneic SCT	NCT04217278	Acute Myeloid L... High-risk Myelo...	Vyxeos Fludarabine Busulphan Thiotepa Cytarabine	18 Years -	University of Birmingham
Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin	NCT00915811	Myelodysplastic... Leukemia, Myelo...	Fludarabine Busulphan Thymoglobuline ... Haematopoietic ...	18 Years -	King's College Hospital NHS Trust

Spots Global Cancer Trial Database for busulphan

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Spots Global Cancer Trial Database for busulphan

Every month we try and update this database with for busulphan cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for busulphan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.