NCT00222612

Brief 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. 1.Can treatment be reduced without compromising efficacy in a MRD-defined low risk group?
  2. 2.Does further post-remission intensification improve outcome for a MRD-defined high risk group?
  3. 3.Measure the Quality of Life impact of the different treatment arms on the children and their families.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
2,100

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Oct 2003

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2003

Completed
2 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 22, 2005

Completed
7.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
Last Updated

February 3, 2010

Status Verified

February 1, 2010

Enrollment Period

9.8 years

First QC Date

September 13, 2005

Last Update Submit

February 2, 2010

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

  • Event free survival

    5 years

Secondary Outcomes (2)

  • Survival

    5 years

  • Quality of life

    3 years

Study Arms (3)

A or B with 2DI

ACTIVE COMPARATOR

3 or 4 drug induction plus 2 delayed intensifications

Drug: Standard childhood UK ALL protocol

C plus 2DI

EXPERIMENTAL

Intensified treatment including Capizzi maintenance

Drug: Intensified treatment including Capizzi maintenance

A or B with 1DI

EXPERIMENTAL

Reduced intensity treatment

Other: Reduced intensification

Interventions

Reduced intensificationOTHER

Deletion of one 7 week treatment block containing dexamethasone, vincristine, doxorubicin, Peg-asparaginase, intrathecal methotrexate, cyclophosphamide, cytarabine.

Also known as: Removal of second delayed intensification
A or B with 1DI
Standard childhood UK ALL protocolDRUG

No additional treatment to standard protocol.

A or B with 2DI
Intensified treatment including Capizzi maintenanceDRUG

Augmented consolidation: vincristine, Peg-asparaginase. Capizzi maintenance: iv methotrexate and peg-asparaginase

C plus 2DI

Eligibility Criteria

Age1 Year - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Children aged 1 - 18 years with ALL except the following:

You may not qualify if:

  • 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.
  • 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.
  • 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.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sheffield Children's Hospital

Sheffield, S10 2TH, United Kingdom

RECRUITING

Related Publications (2)

  • 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.

    PMID: 35714315DERIVED

  • Wilson 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.

    PMID: 19951974DERIVED

Related Links

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Ajay Vora

    Sheffield Children's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan Richards, D Phil

CONTACT

Sue.Richards@ctsu.ox.ac.uk

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 22, 2005

Study Start

October 1, 2003

Primary Completion

August 1, 2013

Study Completion

August 1, 2013

Last Updated

February 3, 2010

Record last verified: 2010-02

Locations

GB(1)