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Trial Details
Trial status:
In set-up (funded)
Recruitment start date:
Funder:
Cancer Research UK
Sponsor:
University of Milano-Bicocca
Chief Investigator:
Dr Michelle Cummins (UK Lead investigator)
Recruitment target:
700 (60 from UK)
EudraCT number:
2017-000705-20
Contact details:
ctc.esphall@ucl.ac.uk
Lay summary:
EsPhALL2017
International phase 3 trial in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) testing imatinib in combination with two different cytotoxic chemotherapy backbones
Description
Design: Eligible patients will be registered into the study during their induction chemotherapy, once their Philadelphia chromosome status has been confirmed.
All patients will have EsPhALL induction chemotherapy + imatinib. At the end of induction IB they will have a bone marrow aspirate, which will undergo minimal residual disease (MRD) testing. MRD results will be used to assign patients to a risk group. 
Standard Risk patients (low MRD) will be randomised to either EsPhALL chemotherapy + imatinib (standard treatment) or the less intensive COG chemotherapy + imatinib (experimental treatment). Treatment lasts 2 years in total.
High Risk patients (high MRD) will continue with EsPhALL chemotherapy + imatinib followed by a stem cell transplant, usually after 1-2 phases of post-induction chemotherapy. Consenting patients who have stem cell transplant will have daily imatinib from day +56 post transplant until day +365 post transplant (experimental treatment)

Patients will be followed up for a minimum of 3 years after completing treatment.

Patients/their families will be asked permission for their samples stored at the Blood Cancer UK Cellbank to be accessed for use in research related to the trial to improve understanding of paediatric Philadelphia positive acute lymphoblastic leukaemia
Treatment: All patients:
EsPhALL induction backbone chemotherapy + imatinib (standard treatment). 
Bone marrow aspirate after induction IB for minimal residual disease (MRD) testing; results used to assign patient to risk group:

Standard risk patients (low MRD after induction IB)
  • EsPhALL backbone chemotherapy + imatinib (standard treatment): consolidation (9 weeks), delayed intensification 1 (8 weeks), interim maintenance (4 weeks), delayed intensification 2 (7 weeks), maintenance (until 2 years treatment completed)
  • COG backbone chemotherapy + imatinib (experimental treatment): interim maintenance 1 (9 weeks), delayed intensification (8 weeks), interim maintenance 2 (8 weeks), maintenance (until 2 years treatment completed)
High risk patients (high MRD levels after induction IB)
Continue with EsPhALL backbone chemotherapy followed by allogeneic stem cell transplant (standard treatment; typically proceed to transplant after consolidation or delayed intensification if patient fit, donor available and adequate disease response)
For patients who have stem cell transplant: daily imatinib from day +56 post transplant to day +365 post transplant (experimental treatment)
Key inclusion/exclusion criteria:

Inclusion Criteria:

1.     Diagnostic bone marrow samples available to develop an MRD probe

2.     Age >1 year and ≤21 years old

3.     Newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukaemia (MPAL) with definitive evidence of BCR-ABL1 fusion by karyotype, FISH and/or RT-PCR

4.     Patient must have started induction therapy including vincristine, a corticosteroid, usually PEG-L-asparaginase, with or without anthracycline and/or other standard cytotoxic chemotherapy

5.     Patient has not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine

6.     Patient may have started imatinib prior to study entry, but has not received more than 14 days of imatinib

7.     ECOG performance status 0-2

8.     Adequate liver function:

-       Direct bilirubin ≤2.0 mg/dl

9.     Adequate cardiac function:

-       Shortening fraction of ≥27% by echocardiogram, or

-       Ejection fraction of ≥50% by radionuclide angiogram or echocardiogram

-       Corrected QT Interval, QTc

10.  Adequate renal function

-       Creatinine clearance or radioisotope GFR ≥70ml/min/1.73m2or

-       Serum creatinine within normal limits forage/gender

Exclusion criteria

1.     Known history of chronic myeloid leukaemia (CML)

2.     ALL developing after a previous cancer treated with cytotoxic chemotherapy

3.     Active, uncontrolled infection or active systemic illness that requires ongoing vasosupressor support or mechanical ventilation

4.     Down syndrome

5.     Pregnancy and breast feeding:

-       Female patients who are pregnant (pregnancy test required for WOCBP)

-       Lactating females who plan to breastfeed their infant

-       Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

6.     Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block

7. Prior treatment with dasatinib, or any BCR-ABL1inhibitor other than imatinib

Duration of recruitment: 4 years
Aim
Standard risk question: To establish whether a less intensive treatment regimen (COG chemotherapy + imatinib) can provide good disease control for Philadelphia positive ALL while reducing the treatment-related toxicity

High risk question: To establish whether it is possible to deliver post-transplant imatinib, and whether this helps to prevent relapse of Philadelphia positive ALL in patients with a higher risk of relapse
Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
Contact Us
Cancer Research UK & UCL Cancer Trials Centre
University College London
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London
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Telephone:
+44 (0)20 7679 9898 (General CTC Enquiries)
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020 7679 9899
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