SPIRIT 2 - STI571

Trial overview

SPIRIT 2 - STI571 Prospective International RandomIsed Trial 2 - A phase III, prospective randomised comparison of imatinib (STI571, Glivec/Gleevec) 400mg daily versus dasatinib 100mg in patients with newly-diagnosed chronic phase chronic myeloid leukaemia.

Inclusion criteria

1. Male or female patients ≥ 18 years of age.

2. Patients must have all of the following:

i) be enrolled within 3 months of initial diagnosis of CML-CP (date of initial
diagnosis is the date of first cytogenetic analysis),

ii) cytogenetic confirmation of the Philadelphia chromosome or variants of (9;22) translocations; patients may have secondary chromosomal
abnormalities in addition to the Philadelphia chromosome.

iii)
(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

iv) no evidence of extramedullary leukaemic involvement, with the exception of hepatosplenomegaly.

3. Written voluntary informed consent.

Exclusion criteria

1. Patients with Ph-negative, BCR-ABL-positive, disease are NOT eligible for the study.

2. Any prior treatment for CML with: any tyrosine kinase inhibitor (eg
imatinib, dasatinib, nilotinib); busulphan; interferon-alpha;
homoharringtonine; cytosine arabinoside; any other investigational agents (hydroxycarbamide and anagrelide are the only drugs permitted). NB patients will be ineligible for the study if they have received ANY prior therapy with interferon-alpha or imatinib. NO exceptions.

3. Patients who received prior chemotherapy, including regimens used in peripheral blood progenitor cells (PBPCs) mobilisation for haematopoietic progenitor-cell transplantation. (It is allowable to collect unmobilised PBPCs at diagnosis.)

4. Patient who have had any form of prior haemopoietic stem cell transplant, either autograft or allograft.

5. Patients with an ECOG Performance Status Score ≥ 3.

6. Patients with serum bilirubin, SGOT/AST, SGPT/ALT, or creatinine
concentrations > 2.0 x the institutional upper limit of the normal range (IULN).

7. Patients with International normalised ratio (INR) or partial
thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulants.

8. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina, or Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria.

9. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required.

10. Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery.

11. Patients who are:

(a) pregnant,
(b) breast feeding,
(c) of childbearing potential without a negative pregnancy test prior to Study Day 1, and (d) male or female of childbearing potential unwilling to use barrier contraceptiveprecautions throughout the trial (postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential).

12. Patients with a history of another malignancy either currently or within the past five years, with the exception of basal cell skin carcinoma or cervical carcinoma in situ.

13. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.