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Acute Lymphoblastic LeukemiaPhase 2ALL-RICNCT03821610

A Comparison of Reduced Dose Total Body Irradiation (TBI) and Cyclophosphamide With Fludarabine and Melphalan Reduced Intensity Conditioning in Adults With Acute Lymphoblastic Leukaemia (ALL) in Complete Remission. (ALL-RIC)

A Phase 2 study testing Fludarabine, Melphalan and Alemtuzumab in people with Acute Lymphoblastic Leukemia, run by University of Birmingham at 22 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The current national acute lymphoblastic leukaemia (ALL) trial in adults investigated whether a low (reduced) intensity chemotherapy regimen prior to transplant could improve the outcome of patients with ALL who are over 40 years of age. Read more about this study

Who is it for?
Ages 40 to 70 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Fludarabine, Melphalan and Alemtuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
242 participants
Where
22 sitesUnited Kingdom
Study dates
22 Nov 2018to 22 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients between the ages of 40-70 years. NB: Patients under the age of 40 who are considered unsuitable for a myeloablative transplant may enrol onto the trial following discussion with the CI via the Trials Office
  • Patients with ALL in first or second CR
  • Availability of a human leukocyte antigen (HLA) identical sibling or suitable matched donor (suitable matched defined as no greater than a single allele mismatch at HLA A, B, C or DRβ1). A single allele mismatch is permitted if there are adverse cytogenetics or MRD positivity at any timepoint
  • Patients considered suitable to undergo a RIC allogeneic SCT as clinically judged by the Local Investigator including:-
  • Adequate hepatic and renal function as determined by full blood count and biochemistry assessment
  • Resolution of any toxic effects of prior therapy (including radiotherapy, chemotherapy or surgical procedures). Patients with bone marrow suppression following therapy may enter the trial
Show all 11Show fewer
  • Patients with abnormal cardiac and/or pulmonary function must be considered fit for allogeneic SCT including 8Gy of TBI at the time of randomisation.
  • Patients with an ECOG performance status 0,1 or 2
  • Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must use appropriate, highly effective, contraception from the point of admission for transplant conditioning therapy until 12 months after transplant (see section 8.1.2.2)
  • Patients have given written informed consent
  • Patients willing and able to comply with scheduled study visits and laboratory tests

Who cannot join

  • Patients with contraindications to receiving RIC allogeneic SCT
  • Female patients who are pregnant or breastfeeding. All women of childbearing potential (WOCBP) must have a negative pregnancy test before commencing treatment
  • Adults of reproductive potential not willing to use appropriate, effective, contraception during the specified period
  • Patients with renal or hepatic impairment as clinically judged by Local Investigator
  • Patients with active infection, HIV-positive or chronic active Hep-A or -C
  • Patients with concurrent active malignancy. Patients with a previous history of malignancy can be included if that malignancy is considered to be at a low risk of recurrence
  • Previous exposure to a high dose of radiotherapy

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United Kingdom22 sites

  • Heart of England Nhs Foundation Trust

    Birmingham, B95ST

  • University Hospitals Birmingham Nhs Foundation Trust

    Birmingham

  • University Hospitals Bristol Nhs Foundation Trust

    Bristol, BS13NU

  • Cambridge University Hospitals Nhs Foundation Trust

    Cambridge, CB20QQ

  • Cardiff and Vale University Health Board

    Cardiff, CF144XW

  • NHS Greater Glasgow and Clyde

    Glasgow, G12 0YN

  • Leeds Teaching Hospitals Nhs Trust

    Leeds, LS9 7TF

  • University Hospitals of Leicester Nhs Trust

    Leicester, LE15WW

  • The Clatterbridge Cancer Centre Nhs Foundation Trust

    Liverpool, CH634JY

  • Barts Health Nhs Trust

    London, E11BB

  • University College London Hospitals Nhs Foundation Trust

    London, NW12PG

  • Kings College Hospital

    London, SE5 9RS

  • The Royal Marsden Nhs Foundation Trust

    London, SW3 6JJ

  • Imperial College Healthcare Nhs Trust

    London, W21NY

  • The Christie Nhs Foundation Trust

    Manchester, M204BX

  • Central Manchester University Hospitals Nhs Foundation Trust

    Manchester

  • The Newcastle Upon Tyne Hospitals Nhs Foundation Trust

    Newcastle

  • Nottingham University Hospitals Nhs Trust

    Nottingham, NG72UH

  • Oxford University Hospitals Nhs Foundation Trust

    Oxford, OX3 9DU

  • Plymouth Hospitals Nhs Trust

    Plymouth, PL68DH

  • Sheffield Teaching Hospitals Nhs Foundation Trust

    Sheffield, S57AU

  • University Hospital Southampton Nhs Foundation Trust

    Southampton, SO16 6YD

Other trials in United Kingdom

About this study

The current national acute lymphoblastic leukaemia (ALL) trial in adults investigated whether a low (reduced) intensity chemotherapy regimen prior to transplant could improve the outcome of patients with ALL who are over 40 years of age. The results (60% 2 year survival) are very encouraging but patients who come to transplant with small amounts of 'residual' disease had less good outcomes. The goal of this trial is to see if a slightly stronger chemotherapy regimen (involving total body irradiation, (TBI)) can improve results by reducing the chance of the disease coming back (relapsing) without increasing the chance of not surviving the transplant. Up to 242 patients will be 'randomised' to the trial to receive either the established chemotherapy of fludarabine and melphalan or cyclophosphamide and TBI to compare the outcomes between the two treatment regimens. Other measures to reduce relapse will be the earlier use of donor white cell infusions and earlier stopping of immune suppressive drugs to enhance the immune effect of the transplanted cells (graft). Patients will be followed up for a minimum of 3 years. All patients on the next national ALL trial (UKALL XV) will be offered this trial but it will also be open to patients not on this study.

Read the detailed description

TRIAL SYNOPSIS

Trial Design This is a 2 arm, phase II, multicentre, randomised clinical trial in adult patients with ALL in complete remission (CR) undergoing allogeneic stem cell transplantation (SCT) comparing the novel conditioning regimen of TBI and cyclophosphamide with the standard condition of Fludarabine/Melphalan/Alemtuzumab (FMA).

Patient will be stratified at randomisation by the donor type (sibling; suitable matched), CR status (CR1; CR2) and by age (above; below 55 years of age). Patients eligible for entry into the trial will be randomised on a 1:1 basis to receive either the experimental treatment arm or the control arm.

Objectives Primary Objectives To compare the disease free survival (DFS) at two years of patients with ALL after a TBI and cyclophosphamide allograft with that of patients transplanted using the FMA conditioning regimen.

Secondary Objectives To compare overall survival (OS), cumulative incidence of disease relapse (CIR), non-relapse mortality (NRM), incidence of grade 2-4 acute graft-versus-host-disease (GvHD), incidence of chronic GvHD of any grade, occurrence and severity of veno-occlusive disease (VOD), duration of hospitalisation in the first year, quality of life (QoL), full donor chimerism at day 100 and TBI related symptomatic pulmonary toxicity between the control and experimental arm following allogenic SCT.

Exploratory Objectives To measure multi-lineage chimerism and molecular minimal residual disease (MRD) at 3 monthly intervals and the ability of planned donor lymphocyte infusion (DLI) to 'correct' mixed chimerism and reverse molecular relapse/persistence and reduce the incidence of frank haematologic relapse.

To ascertain if either of the conditioning arms is more effective in controlling disease in patients who are MRD positive before transplant.

Patient Population This trial will recruit patients with ALL in CR as defined by the WHO classification (Appendix 1). Patients enrolled onto the UKALL XIV registration study and the planned national UKALL XV study who are eligible for transplant will also be able to enrol onto ALL-RIC provided they meet the entry criteria.

Sample Size A minimum of 247 patients will be randomised 1:1 between the control and experimental treatment arms.

Trial Duration Patients will be recruited over 48 months across IMPACT centres. Patients will be followed up for a minimum of 5 years.

Being tested
Fludarabine, Melphalan, Alemtuzumab, Cyclophosphamide, Mesna
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03821610
Study groupRoleWhat they receive
Fludarabine / Melphalan / AlemtuzumabActive comparatorDay -7 Fludarabine 30mg/m2 od IV Day -6 Fludarabine 30mg/m2 od IV Day -5 Fludarabine 30mg/m2 od IV Day -4 Fludarabine 30mg/m2 od IV Day -3 Fludarabine 30mg/m2 od IV Day -2 Melphalan 140mg/m2 od IV, Alemtuzumab 20 mg od IV (unrelated transplants only) Day -1 Alemtuzumab 20mg od IV Day 0 Infusion of sibling or unrelated donor peripheral blood stem cells
Receives: Drug: Fludarabine; Drug: Melphalan; Drug: Alemtuzumab
Cyclophosphamide / TBI (8Gy)ExperimentalDay -6 Cyclophosphamide 50 mg/kg od IV , Mesna 20 mg/kg od IV, Mesna 76mg/kg od IV Day -5 Cyclophosphamide 50 mg/kg od IV, Mesna 20 mg/kg od IV, Mesna 76 mg/kg od IV Day -4 Rest Day -3 TBI (2Gy) bd Day -2 TBI (2Gy) bd, Alemtuzumab 20mg od IV (unrelated transplants only) Day -1 Alemtuzumab 20mg od IV Day 0 Infusion of sibling or unrelated donor peripheral blood stem cells or bone marrow
Receives: Drug: Alemtuzumab; Drug: Cyclophosphamide; Drug: Mesna; Radiation: Total Body Irradiation (8Gy)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival (DFS)

    Defined as time from randomisation to the first of relapse or death from any cause. Patients who are still alive and progression free at the end of the trial will be censored at their last date known to be alive.

    Measured: The main analysis will take place once all patients have completed 2 years of follow up.

Secondary outcomes (10)

  1. Overall Survival (OS)

    Defined as time from randomisation to date of death from any cause. Patients who are alive at the end of the trial will be censored at their date last known to be alive

    Measured: The main analysis will take place once all patients have completed 2 years of follow up. A subsequent analysis of long terms outcomes will be completed when all patients have completed 5 years of follow up

  2. Cumulative Incidence of Relapse (CIR)

    Defined as time from randomisation to the date of relapse. Patients who die without 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 as their date last seen

    Measured: The main analysis will take place once all patients have completed 2 years of follow up. A subsequent analysis of long terms outcomes will be completed when all patients have completed 5 years of follow up

  3. Non-relapse mortality (NRM)

    Defined as time from randomisation to death from any cause that occurred without relapse. Patients who relapse will be treated as a competing risk and patients who are still alive and relapse free at the end of the trial will be censored at their date last known to be aliveIncidence of Grade 2-4 acute GvHD within 100 days of transplant

    Measured: The main analysis will take place once all patients have completed 2 years of follow up. A subsequent analysis of long terms outcomes will be completed when all patients have completed 5 years of follow up

  4. Incidence of chronic GvHD of any grade at 2 years

    Measured: The main analysis will take place once all patients have completed 2 years of follow up. A subsequent analysis of long terms outcomes will be completed when all patients have completed 5 years of follow up

  5. Occurrence and severity of VOD (Veno-occlusive disease) in the first 100 days

    Measured: The main analysis will take place once all patients have completed 2 years of follow up. A subsequent analysis of long terms outcomes will be completed when all patients have completed 5 years of follow up

  6. Duration of hospitalisation

    Duration of hospitalisation recorded between start of conditioning regimen and 1 year post transplantation.

    Measured: The outcome will be conducted when all patients have completed 1 year of follow up.

  7. Quality of Life (QoL) assessment (FACT-BMT Questionnaire)

    FACT-BMT Questionnaire uses Units on a scale 0-4. It measures quality of life, with 0 being the lowest quality of life and 4 being the highest quality of life.

    Measured: Collected at baseline, Day 100, Month 12, Month 24, Month 36, Month 48 and Month 60 for each patient. The outcome will be analysed when the last patient has completed 2 years of follow up.

  8. Quality of Life (QoL) assessment (Short Form 36 Health Survey)

    Short Form 36 Health Survey uses Units on a scale 1-6. Question 1 \& 2 consider general health (1 = best health score, 5 = worst). Question 3 considers activity level (1= least active, 3 = most). Question 4/5 considers work (1= work affected, 2= work not affected). Question 6 considers quality of relationships (1=not affected, 5 = most affected). Question 7 considers pain (1= no pain, 6 = worst). Question 8 considers housework/ paid work (1= not affected, 5= most affected). Question 9 considers mental health (1= best mental health, 6= worst). Question 10 considers social activities (1=most affected, 5= least affected). Question 11 considers self perception (1= worst, 5= best)

    Measured: Collected at baseline, Day 100, Month 12, Month 24, Month 36, Month 48 and Month 60 for each patient. The outcome will be analysed when the last patient has completed 2 years of follow up.

  9. Full donor chimerism

    Number of patients with full donor chimerism at day 100 Follow Up (for each patient)

    Measured: The outcome will be analysed when all patients have completed 100 days follow up.

  10. Occurrence and severity of TBI related symptomatic pulmonary toxicity

    Collected using CTCAE 4.0 criteria

    Measured: Collected in first 12 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2019
  2. Study start22 Nov 2018
  3. Primary completion31 Oct 2025
  4. Study completion22 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
242 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03821610
Sponsor's protocol ID
RG_17-241
Acronym
ALL-RIC
Status last verified
Apr 2026
First submitted
9 Jan 2019
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Melphalan and Alemtuzumab in people with Acute Lymphoblastic Leukemia, run by University of Birmingham at 22 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (DFS) (time frame: The main analysis will take place once all patients have completed 2 years of follow up.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03821610.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.

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