Acute Lymphoblastic LeukemiaPhase 4NCT00222612
Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
A Phase 4 study testing Reduced intensification, Standard childhood UK ALL protocol and Intensified treatment including Capizzi maintenance in people with Acute Lymphoblastic Leukemia, run by University of Oxford at 1 site in United Kingdom.
Trial summary
A randomised trial for children with acute lymphoblastic leukemia, using the detection of minimal residual disease to define risk groups, aiming to answer the questions: 1. Can treatment be reduced without compromising efficacy in a MRD-defined low risk group? 2. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Reduced intensification, Standard childhood UK ALL protocol and Intensified treatment including Capizzi maintenance
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2003to Aug 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children aged 1 - 18 years with ALL except the following:
- Standard or Intermediate Risk as defined above.
- Morphological Complete Remission (BM1 Marrow) at Day 29 of Induction.
- Availability of MRD results at Day 28 and after consolidation therapy.
- Informed consent obtained.
- Induction given as protocol.
Who cannot join
- Infants less than a year old should be entered onto the Interfant ALL study.
- Children with B-ALL (Burkitt-like, t(8;14), L3 morphology, SMIg positive). Patients with this disease will be eligible for the current UKCCSG B cell NHL/ALL trial.
- Children with Philadelphia-positive ALL (t(9;22) or BCR/ABL positive) will start induction therapy on this protocol but transfer to the European Intergroup Protocol as soon as their Philadelphia status is known.
- Initially, eligible patients will be stratified into three risk groups based on the following criteria:
- Standard risk: all children >1<10 years with a highest white cell count before starting treatment of <50x109/l, and who do not have BCR-ABL, hypodiploidy (≥44 chromosomes), or an MLL gene rearrangement.
- Intermediate risk: all children ≥10 years old, or with a diagnostic WBC ≥50x109/l (or both) and who do not have BCR-ABL, hypodiploidy (≥44 chromosomes), or an MLL gene rearrangement.
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- High Risk: all children, irrespective of initial risk category, who have a slow early response (SER) as defined below - see section 6 - together with those who have BCR-ABL (induction only), hypodiploidy (≥44 chromosomes), or an MLL gene rearrangement. These patients will not be eligible for MRD randomisation.
- Patients will then start treatment according to their risk group as follows:
- Standard risk, (around 60-65% of the total): regimen A - three-drug induction.
- Intermediate risk, (around 20- 30% of the total): regimen B - four-drug induction.
- High risk (around 10-12% of the total): These patients will not be eligible for MRD randomisation. They will be allocated regimen C - four drug induction, augmented BFM consolidation, Capizzi interim maintenance, and two further BFM-style intensification periods of extended duration.
- High Risk as defined above. These patients will receive Regimen C.
- Day 28 non-remitters. These patients will receive Regimen C if BM2 or go off-protocol if BM3 (see below for definitions of BM2 and BM3).
- MRD Indeterminate Group (No result or MRD positive < 1 x 10-4 at day 28 and after consolidation therapy) will continue on previously assigned therapy.
- Sub-optimal induction therapy. The clinical significance of day 28 MRD is uncertain in patients who have received sub-optimal induction therapy. Please discuss these patients with a co-ordinator.
Trial locations and contacts
1 site in 1 country.
Susan Richards, D Phil contact
United Kingdom1 site, 1 recruiting
- Recruiting
Sheffield Children's Hospital
Sheffield, S10 2TH
Ajay Vora, ajay.vora@sch.nhs.uk
About this study
Official title: Medical Research Council Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
A randomised trial for children with acute lymphoblastic leukemia, using the detection of minimal residual disease to define risk groups, aiming to answer the questions:
- Can treatment be reduced without compromising efficacy in a MRD-defined low risk group?
- Does further post-remission intensification improve outcome for a MRD-defined high risk group?
- Measure the Quality of Life impact of the different treatment arms on the children and their families.
Read the detailed description
Randomisations
Patients will be assigned to MRD risk groups based on day 29 and post consolidation MRD results and randomised as follows:
- MRD Low Risk Group (MRD negative at day 29 and week 11 or positive <1 x 10-4 at day 28 and negative at week 11) will continue on previously assigned Regimens (A or B) but randomised between two delayed intensifications and one delayed intensification.
- MRD High Risk Group (MRD positive > 1 x 10-4 at day 29) randomised between previously assigned Regimen (A or B) and Regimen C.
- MRD Indeterminate Group (No MRD result or MRD positive <1 x 10-4 at day 29 and at week 11) will continue on previously assigned Regimen (A or B) and received two delayed intensifications
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Reduced intensification, Standard childhood UK ALL protocol, Intensified treatment including Capizzi maintenance
- 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.
Reduced intensificationOther
Also called Removal of second delayed intensification
Deletion of one 7 week treatment block containing dexamethasone, vincristine, doxorubicin, Peg-asparaginase, intrathecal methotrexate, cyclophosphamide, cytarabine.
Standard childhood UK ALL protocolDrug
No additional treatment to standard protocol.
Intensified treatment including Capizzi maintenanceDrug
Augmented consolidation: vincristine, Peg-asparaginase. Capizzi maintenance: iv methotrexate and peg-asparaginase
| Study group | Role | What they receive |
|---|---|---|
| A or B with 2DI | Active comparator | 3 or 4 drug induction plus 2 delayed intensifications Receives: Drug: Standard childhood UK ALL protocol |
| C plus 2DI | Experimental | Intensified treatment including Capizzi maintenance Receives: Drug: Intensified treatment including Capizzi maintenance |
| A or B with 1DI | Experimental | Reduced intensity treatment Receives: Other: Reduced intensification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival
Measured: 5 years
Secondary outcomes (2)
Survival
Measured: 5 years
Quality of life
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startOct 2003
- Primary completionAug 2013 (estimated)
- Study completionAug 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Investigators
- Ajay Vora, Principal investigator, Sheffield Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00222612
- Sponsor's protocol ID
- UKALL2003
- Status last verified
- Feb 2010
- First submitted
- 13 Sep 2005
- Last updated
- 3 Feb 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Moorman AV, Antony G, Wade R, Butler ER, Enshaei A, Harrison CJ, Moppett J, Hough R, Rowntree C, Hancock J, Goulden N, Samarasinghe S, Vora A. Time to Cure for Childhood and Young Adult Acute Lymphoblastic Leukemia Is Independent of Early Risk Factors: Long-Term Follow-Up of the UKALL2003 Trial. J Clin Oncol. 2022 Dec 20;40(36):4228-4239. doi: 10.1200/JCO.22.00245. Epub 2022 Jun 17.
PubMed 35714315Wilson K, Case M, Minto L, Bailey S, Bown N, Jesson J, Lawson S, Vormoor J, Irving J. Flow minimal residual disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34+CD38lowCD19+ in B-lineage childhood acute lymphoblastic leukemia. Haematologica. 2010 Apr;95(4):679-83. doi: 10.3324/haematol.2009.011726. Epub 2009 Nov 30.
PubMed 19951974
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Medical Research Council Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
- ClinicalTrials.gov ID
- NCT00222612
- Acronym / sponsor ID
- UKALL2003
- Conditions
- Acute Lymphoblastic Leukemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,100 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- Oct 2003
- Primary completion
- Aug 2013 (estimated)
- Study completion
- Aug 2013 (estimated)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomised trial for children with acute lymphoblastic leukemia, using the detection of minimal residual disease to define risk groups, aiming to answer the questions:
- Can treatment be reduced without compromising efficacy in a MRD-defined low risk group?
- Does further post-remission intensification improve outcome for a MRD-defined high risk group?
- Measure the Quality of Life impact of the different treatment arms on the children and their families.
Detailed description
Randomisations
Patients will be assigned to MRD risk groups based on day 29 and post consolidation MRD results and randomised as follows:
- MRD Low Risk Group (MRD negative at day 29 and week 11 or positive <1 x 10-4 at day 28 and negative at week 11) will continue on previously assigned Regimens (A or B) but randomised between two delayed intensifications and one delayed intensification.
- MRD High Risk Group (MRD positive > 1 x 10-4 at day 29) randomised between previously assigned Regimen (A or B) and Regimen C.
- MRD Indeterminate Group (No MRD result or MRD positive <1 x 10-4 at day 29 and at week 11) will continue on previously assigned Regimen (A or B) and received two delayed intensifications
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A or B with 2DI | Active comparator | Drug: Standard childhood UK ALL protocol3 or 4 drug induction plus 2 delayed intensifications |
| C plus 2DI | Experimental | Drug: Intensified treatment including Capizzi maintenanceIntensified treatment including Capizzi maintenance |
| A or B with 1DI | Experimental | Other: Reduced intensificationReduced intensity treatment |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Standard or Intermediate Risk as defined above.
- Morphological Complete Remission (BM1 Marrow) at Day 29 of Induction.
- Availability of MRD results at Day 28 and after consolidation therapy.
- Informed consent obtained.
- Induction given as protocol.
Key exclusion criteria (15 listed)
- Infants less than a year old should be entered onto the Interfant ALL study.
- Children with B-ALL (Burkitt-like, t(8;14), L3 morphology, SMIg positive). Patients with this disease will be eligible for the current UKCCSG B cell NHL/ALL trial.
- Children with Philadelphia-positive ALL (t(9;22) or BCR/ABL positive) will start induction therapy on this protocol but transfer to the European Intergroup Protocol as soon as their Philadelphia status is known.
- Initially, eligible patients will be stratified into three risk groups based on the following criteria:
- Standard risk: all children >1<10 years with a highest white cell count before starting treatment of <50x109/l, and who do not have BCR-ABL, hypodiploidy (≥44 chromosomes), or an MLL gene rearrangement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced intensificationAlso: Removal of second delayed intensificationDeletion of one 7 week treatment block containing dexamethasone, vincristine, doxorubicin, Peg-asparaginase, intrathecal methotrexate, cyclophosphamide, cytarabine. | Other | A or B with 1DI |
| Standard childhood UK ALL protocolNo additional treatment to standard protocol. | Drug | A or B with 2DI |
| Intensified treatment including Capizzi maintenanceAugmented consolidation: vincristine, Peg-asparaginase. Capizzi maintenance: iv methotrexate and peg-asparaginase | Drug | C plus 2DI |
Primary outcome
Event free survival
Time frame: 5 years
2 secondary outcomes
Survival
Time frame: 5 years
Quality of life
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2010.
- Derived from this study: PubMed 35714315Moorman AV, Antony G, Wade R, Butler ER, Enshaei A, Harrison CJ, Moppett J, Hough R, Rowntree C, Hancock J, Goulden N, Samarasinghe S, Vora A. Time to Cure for Childhood and Young Adult Acute Lymphoblastic Leukemia Is Independent of Early Risk Factors: Long-Term Follow-Up of the UKALL2003 Trial. J Clin Oncol. 2022 Dec 20;40(36):4228-4239. doi: 10.1200/JCO.22.00245. Epub 2022 Jun 17.
- Derived from this study: PubMed 19951974Wilson K, Case M, Minto L, Bailey S, Bown N, Jesson J, Lawson S, Vormoor J, Irving J. Flow minimal residual disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34+CD38lowCD19+ in B-lineage childhood acute lymphoblastic leukemia. Haematologica. 2010 Apr;95(4):679-83. doi: 10.3324/haematol.2009.011726. Epub 2009 Nov 30.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Richards, D Phil contact
Ajay Vora principal investigator
Sheffield Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Reduced intensification, Standard childhood UK ALL protocol and Intensified treatment including Capizzi maintenance in people with Acute Lymphoblastic Leukemia, run by University of Oxford at 1 site 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 6 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 3 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Susan Richards, D Phil (Sue.Richards@ctsu.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (time frame: 5 years). 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 NCT00222612, which also lists 2 linked publications.
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 3 Feb 2010.