Transcript SPIRIT - Site Initiation Overview

STI571 Prospective International RandomIsed Trial
A phase III, prospective randomised comparison of imatinib (STI571,
Glivec/Gleevec) 400mg daily versus imatinib 800mg daily versus
imatinib plus PEGinterferon-alpha 2a (Pegasys) in patients with
newly-diagnosed chronic-phase chronic myeloid leukaemia.
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SPIRIT CML Trial Overview
Contents
• Key Facts
• Study Summary
• Patient recruitment
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Inclusion criteria
Consent Forms
Randomisation
Study Schedule
AE’s and SAE’s
PCR analysis
Treatment arm details
Further Information
– Website
– Forms
• eCRF system training
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SPIRIT CML Trial Overview
Key Facts
• NCRN Adopted study
• UK Multicentre study
• Versions running also in GE and FR - may combine
data
• Looking for 2466 patients from UK
• Current situation
– First patient recruited June 2005
– 96 sites now with ethics approval
– 248 patients randomised
• Electronic Data Capture via internet
• Website: www.spirit-cml.org
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SPIRIT CML Trial Overview
Study Summary
• Randomised, Open label
• Newly Diagnosed CML (within 3 months)
• 2 treatment arms (822 patients on each)
– Arm A:
– Arm B:
– Arm C:
400mg daily imatinib
800mg daily imatinib
closed 21 Feb 2008
• Arm C: 400mg daily imatinib plus up to 180mg weekly
PEGinterferon a
• Primary end point is survival at 5 years
• Secondary endpoints include haematologic and
cytogenetic responses
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SPIRIT CML Trial Overview
Patient recruitment
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Inclusion criteria
Consent Forms
Randomisation
Study Schedule
SPIRIT CML Trial Overview
Eligibility - Inclusion Criteria
1. ≥ 18 years old.
2. ALL of the following should apply to patient:
i. within 3 months of initial diagnosis of CML-Chronic Phase,
ii. Received no CML treatment (but hydroxyurea and/or
anagrelide OK),
iii. Patient is Philadelphia chromosome positive,
iv. Patient has
a) < 15% blasts in peripheral blood and bone marrow;
b) < 30% blasts plus promyelocytes in peripheral blood and bone
marrow;
c) < 20% basophils in peripheral blood;
d) ≥ 100 x 109/L platelets;
e) no extramedullary involvement (except hepatosplenomegaly).
3. Written voluntary informed consent.
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SPIRIT CML Trial Overview
Eligibility - Exclusion Criteria (1)
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Patient is Ph-negative, BCR-ABL-positive.
Prior treatment for CML.
Prior chemotherapy (any type).
Prior haemopoietic stem cell transplant, either
autograft or allograft.
ECOG Score ≥ 3.
Serum bilirubin, SGOT/AST, SGPT/ALT, or
creatinine > 2.0 x IULN.
INR or PTT > 1.5 x IULN.
Uncontrolled medical disease.
Prior history of significant psychiatric illness,
particularly depression.
SPIRIT CML Trial Overview
Eligibility - Exclusion Criteria (2)
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HIV-positive (HIV test not required).
Major surgery within 4 weeks of Study Day 1, or
not recovered from prior major surgery.
Patient is:
a. pregnant,
b. breast feeding,
c. without a negative pregnancy test,
d. unwilling to use barrier contraceptive .
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Another malignancy within the past five years.
History of non-compliance to medical regimens or
potentially unreliable.
SPIRIT CML Trial Overview
Informed Consent
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There are 3 consent forms
1. Participation in the SPIRIT Trial
2. Donation of material to CML Biobank
3. CML Patient Registry
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The patient only needs to agree to part (1)
to be included in the trial.
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Remember: Patient Information Sheet and Informed Consent
Forms should be printed on Hospital Headed Paper.
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SPIRIT CML Trial Overview
Randomisation
1. Fax to Trial Manager (0)191 376 0748.
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Signed informed consent form(s)
Cytogenetics report
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Open visit – visit date
Eligibility criteria
Demography
Randomisation (save as complete)
Randomisation – Patient Set-up
2. Create new patient in eCRF
3. Complete screening eCRF pages
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Treatment arm allocation and subject number will
then be displayed on screen.
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SPIRIT CML Trial Overview
Study Schedule (1)
Year 1
• Visit 1
• Visit 2
• Visit 3
• Visit 4
• Visit 5
• Visit 6
• Visit 7
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Screening
Day 28 (1 month)
Day 56 (2 months)
Day 84 (3 months)
6 months
9 months
12 months
Years 2 – 5
• Visits 8 – 15
• Visits every 6 months
SPIRIT CML Trial Overview
Study Schedule (2)
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Visit Date – all visits
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Eligibility
Demography (NHS number)
Medical History
CML Diagnosis Date
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PCR sample – every 3 months
Bone marrow assessment – once a year
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Physical examination
Extramedullary Involvement Liver & Spleen
ECOG Score
Quality of Life Questionnaire
Labs (Haem/Biochem)
Adverse Events
Study medication
Concomitant medications
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Screening only
SPIRIT CML Trial Overview
All visits
AE’s and SAE’s
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Protocol Section 9.3 - discusses Safety Reporting:
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An adverse event is defined as any undesirable sign, symptom, or medical
condition occurring after starting study drug, whether considered study drugrelated or not.
Please ensure that all adverse events (whether related to study drug or not) are
recorded in the patient’s electronic case report form (via the SPIRIT website).
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A serious adverse event is defined as an event that is:
1. fatal, or life-threatening
2. requires or prolongs hospitalization
3. significantly or permanently disabling
4. is a congenital anomaly
5. any other significant medical event
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SAE’s must be faxed to Trial Manager within 24 hours
Fax SPIRIT SAE form to (0)191 376 0748.
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SPIRIT CML Trial Overview
PCR Samples
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PCR analysis - BCR-ABL (secondary endpoint).
Hammersmith Hospital
20 mls peripheral blood - every 3 months.
First PCR sample (visit 1) - PRIOR to imatinib
treatment.
• Please label samples and package clearly as 'SPIRIT
Trial’ and include Shipping Form.
• The samples should be sent via first class post on a
Monday, Tuesday or Wednesday only (to avoid
samples arriving at the weekend and degrading).
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SPIRIT CML Trial Overview
Treatment Arms
Imatinib
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First 400mg daily imatinib in both treatment arms is supplied from
usual NHS stock (as per non-trial patient)
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A SPIRIT Trial label must be applied
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Drug accountability still required – considered IMP
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400mg daily imatinib
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800mg daily imatinib
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No additional supplies required
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Total daily dose made up from 2 sources:
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Is usually taken as 400mg BD
Imatinib trial stock supplied to hospital pharmacy directly from Novartis.
If patient is randomisation to 800mg arm, trial manager will automatically order
a re-supply of trial stock for pharmacy.
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400mg daily supplied from NHS stock
400mg daily supplied from SPIRIT Trial stock
SPIRIT CML Trial Overview
Where to get information
• Trial manager - Corinne Hedgley
 01280 814 916
 [email protected]
• Website - www.spirit-cml.org
 Pharmacy section (information for pharmacists, trial prescription,
dispensing logs etc)
 Study File section (details study file contents, site logs etc)
 Document Centre (protocol, ethical approval and other documents)
 Contact details (Trial Manager, Chief Investigator)
 Newsletter (study updates)
Nov 2008
SPIRIT CML Trial Overview