SPIRIT 3: To evaluate the most effective way to use imatinib, nilotinib and ponatinib in the treatment of chronic myeloid leukaemia
- Conditions
- Chronic myeloid leukaemiaCancerChronic myeloid leukaemia [CML], BCR/ABL-positive
- Registration Number
- ISRCTN60655195
- Lead Sponsor
- ewcastle-upon-Tyne Hospitals NHS Foundation Trust (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 1000
1. Male or female patients who are 18 years of age or over.
2. Patients must fulfill all of the following:
2.1. Be diagnosed with chronic phase chronic myelogenous leukemia (CML) confirmed by blood morphology and reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL.
2.2. Be enrolled within 3 months of initial diagnosis of chronic phase CML (date of RT-PCR confirming presence of BCR-ABL)
2.3. Be in confirmed chronic phase ie:
2.3.1. Less than 15% blasts in blood (manual differential)
2.3.2. Less than 30% blasts plus promyelocytes in blood
2.3.3. Less than 20 % basophils in blood
2.3.4. Less than 100 x 109 /L platelets
2.3.5. No evidence of extramedullary leukaemic involvement, with the exception of hepatosplenomegaly
3. Written voluntary informed consent.
1. Any prior treatment for CML with any tyrosine kinase inhibitors (TKI) (eg imatinib, dasatinib, nilotinib, bosutinib, ponatinib); busulphan, interferon-alpha (IFN-alpha), homoharringtonine, cytosine arabinoside, any other investigational agents.
2. Patients who have received prior CML chemotherapy including regimens used in peripheral blood progenitor cells (PBPCs) mobilisation for haematopoietic progenitor-cell transplantation. (collection of unmobilised PBPCs is allowed at diagnosis).
3. Patients who have had any form of prior haematopoietic stem cell transplant (autograft or allograft).
4. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score = 3
5. Patients with serum bilirubin, SGOT/AST, SGPT/ALT or creatinine concentrations > 2.0 x upper limit of normal (ULN)
6. Patients with serum amylase or lipase > 1.5 x ULN, history of acute pancreatitis within 1 year of study, history of chronic pancreatitis, or uncontrolled hypertriglyceridaemia (triglycerides > 450 mg/dL)
7. Patients with significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to a) myocardial infarction, unstable angina and/or congestive heart failure within 6 months prior to study; and b) history of clinically significant atrial arrhythmia; or any ventricular arrhythmia.
8. Patients taking medications known to be associated with Torsade de Pointes (eg amiodarone, azithromycin, chloroquine, citalopram, domperidone, erythromycin, quinidine, sotalol, thioridazine)
9. Patients with known uncontrolled hypertension; systolic blood pressure > 140mm Hg and/or diastolic blood pressure > 90mm Hg
10. Patients with a known international normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants, or patients with a known bleeding disorder. Baseline testing of INR is not required.
11. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders or infection.
12. Patients who have undergone major surgery within 4 weeks of starting trial investigational medicinal products (IMP).
13. Patients who are:
13.1. Pregnant
13.2. Breast feeding
13.3. Of childbearing potential without a negative pregnancy test prior to starting trial IMP
13.4. Male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential).
14. Patients with a history of another malignancy either currently or within the past five years (with the exception of basal cell skin carcinoma in situ).
15. Patients with a history of non-compliance to medical regimens or patients who can envisage being unable to complete the study for any reason.
16. Patients unwilling to receive trial drug via a home delivery method.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine whether, in terms of major molecular response (MMR, MR3) at three years, first-line treatment with imatinib is non-inferior to first-line treatment with nilotinib when patients on either treatment who are not responding optimally switch to ponatinib.
- Secondary Outcome Measures
Name Time Method 1. To assess survival (OS, PFS and EFS) in group I vs group N at 5 years from study entry.<br>2. To determine what proportions of patients in group I and in group N who have been on study for at least 3 years and who have achieved stable MR3 for at least 2 years can reduce or stop TKI treatment and maintain at least MR3. <br>3. To compare the cost effectiveness over a 5 year period (and projected over the lifetime of the patient) of group I vs group N.