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

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Brief Title

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

Official Title

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

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. 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.
    

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 Phase

Phase 4

Study Type

Interventional


Primary Outcome

Event free survival

Secondary Outcome

 Survival

Condition

Acute Lymphoblastic Leukemia

Intervention

Reduced intensification

Study Arms / Comparison Groups

 A or B with 2DI
Description:  3 or 4 drug induction plus 2 delayed intensifications

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

2100

Start Date

October 2003

Completion Date

August 2013

Primary Completion Date

August 2013

Eligibility Criteria

        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.
      

Gender

All

Ages

1 Year - 18 Years

Accepts Healthy Volunteers

No

Contacts

Ajay Vora, , [email protected]

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT00222612

Organization ID

UKALL2003



Study Sponsor

University of Oxford

Collaborators

 Medical Research Council

Study Sponsor

Ajay Vora, Principal Investigator, Sheffield Children's Hospital


Verification Date

February 2010