SPIRIT2: Comparison of Imatinib Versus Dasatinib in Patients With Newly-diagnosed Chronic Phase Chronic Myeloid Leukaemia

Sponsor

Newcastle University (Other)

Overall Status

Completed

CT.gov ID

NCT01460693

Collaborator

Newcastle-upon-Tyne Hospitals NHS Trust (Other), Bristol-Myers Squibb (Industry), Institute of Cancer Research, United Kingdom (Other), Hammersmith Hospitals NHS Trust (Other)

814

Enrollment

Location

Arms

115.2

Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Imatinib 400mg daily is the current NICE-approved standard treatment for newly diagnosed Chronic Myeloid Leukaemia (CML). 5 yr follow up of CML patients treated in this way indicates an 89% probability of progression-free survival. Imatinib is not tolerated or effective in some patients however, and a proportion of patients become resistant to the drug. SPIRIT 2 study aims to establish whether a new drug, dasatinib, is superior to imatinib in terms of event free survival and therefore will be an effective first-line therapy for newly-diagnosed CML patients. This study will also provide crucial long-term survival, quality of life and health economic data to assist health care providers and managers to determine the most cost-effective drug therapy for CML.

Condition or Disease	Intervention/Treatment	Phase
Myeloid Leukemia, Chronic, Chronic Phase	Drug: Imatinib Drug: Dasatinib	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

814 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2008

Actual Primary Completion Date :

Mar 7, 2018

Actual Study Completion Date :

Mar 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A - Imatinib Imatinib 400mg daily	Drug: Imatinib Oral Imatinib 100mg daily Other Names: Gleevec/Gleevic
Experimental: Arm B - Dasatinib Dasatinib 100mg daily	Drug: Dasatinib Oral Dasatinib 100mg daily Other Names: Sprycel

Arm

Intervention/Treatment

Active Comparator: Arm A - Imatinib

Imatinib 400mg daily

Drug: Imatinib

Oral Imatinib 100mg daily

Other Names:

Gleevec/Gleevic

Experimental: Arm B - Dasatinib

Dasatinib 100mg daily

Drug: Dasatinib

Oral Dasatinib 100mg daily

Other Names:

Sprycel

Outcome Measures

Primary Outcome Measures

5-year event free survival [ongoing throughout study (5 years)]
To compare 5-year event free survival between the 2 treatment arms. The study aim is to show superiority of the dasatinib arm over the imatinib 400mg arm.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients 18 years or over.
Patients must have all of the following:

be enrolled within 3 months of initial diagnosis of CML-CP (date of initial diagnosis is the date of first cytogenetic analysis)
cytogenetic confirmation of the Philadelphia chromosome or variants of (9;22) translocations
patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome.
< 15% blasts in peripheral blood and bone marrow;
< 30% blasts plus promyelocytes in peripheral blood and bone marrow;
< 20% basophils in peripheral blood,
100 x 109/L platelets or greater
no evidence of extramedullary leukaemic involvement, with the exception of the hepatosplenomegaly.

Written voluntary informed consent.

Exclusion Criteria:

Patients with Ph-negative, BCR-ABL-positive, disease are NOT eligible for the study.
Any prior treatment for CML with: any tyrosine kinase inhibitor (eg imatinib, dasatinib); 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.
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.)
Patient who have had any form of prior haemopoietic stem cell transplant, either autograft or allograft.
Patients with an ECOG Performance Status Score of 2 or less.
Patients with serum bilirubin, SGOT/AST, SGPT/ALT, or creatinine concentrations > 2.0 x the institutional upper limit of the normal range (IULN).
Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulants.
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.
Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required.
Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery.
Patients who are:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Freeman Hospital	Newcastle-upon-Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

Newcastle University
Newcastle-upon-Tyne Hospitals NHS Trust
Bristol-Myers Squibb
Institute of Cancer Research, United Kingdom
Hammersmith Hospitals NHS Trust

Investigators

Principal Investigator: Stephen G O'Brien, MD, Newcastle University
Principal Investigator: Richard E Clark, MD, Royal Liverpool University Hospital
Principal Investigator: Jane Apperley, MD, Imperial College London