Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003

February 2, 2010 updated by: University of Oxford

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:

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Randomisations

Patients will be assigned to MRD risk groups based on day 29 and post consolidation MRD results and randomised as follows:

  1. 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.
  2. MRD High Risk Group (MRD positive > 1 x 10-4 at day 29) randomised between previously assigned Regimen (A or B) and Regimen C.
  3. 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 Type

Interventional

Enrollment (Anticipated)

2100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

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

Exclusion criteria:

  1. Infants less than a year old should be entered onto the Interfant ALL study.
  2. 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.
  3. 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:

  1. 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.
  2. 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.
  3. 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:

  1. Standard risk, (around 60-65% of the total): regimen A - three-drug induction.
  2. Intermediate risk, (around 20- 30% of the total): regimen B - four-drug induction.
  3. 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.

Inclusion criteria for entry into the randomisations:

  1. Standard or Intermediate Risk as defined above.
  2. Morphological Complete Remission (BM1 Marrow) at Day 29 of Induction.
  3. Availability of MRD results at Day 28 and after consolidation therapy.
  4. Informed consent obtained.
  5. Induction given as protocol.

Exclusion criteria for entry into the MRD randomisation:

  1. High Risk as defined above. These patients will receive Regimen C.
  2. 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).
  3. 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.
  4. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: A or B with 2DI
3 or 4 drug induction plus 2 delayed intensifications
Drug: Standard childhood UK ALL protocol
No additional treatment to standard protocol.
Experimental: C plus 2DI
Intensified treatment including Capizzi maintenance
Drug: Intensified treatment including Capizzi maintenance
Augmented consolidation: vincristine, Peg-asparaginase. Capizzi maintenance: iv methotrexate and peg-asparaginase
Experimental: A or B with 1DI
Reduced intensity treatment
Other: Reduced intensification
Deletion of one 7 week treatment block containing dexamethasone, vincristine, doxorubicin, Peg-asparaginase, intrathecal methotrexate, cyclophosphamide, cytarabine.
Other Names:
  • Removal of second delayed intensification

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event free survival
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: 5 years
5 years
Quality of life
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Medical Research Council

Investigators

  • Principal Investigator: Ajay Vora, Sheffield Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Primary Completion (Anticipated)

August 1, 2013

Study Completion (Anticipated)

August 1, 2013

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 14, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

February 3, 2010

Last Update Submitted That Met QC Criteria

February 2, 2010

Last Verified

February 1, 2010

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UKALL2003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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