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

NCT01460693 | Completed Phase 3 DMC

• 3 other identifiers: 44432007-006185-15ISRCTN54923521
• Study Type: interventional
• Target: 814
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloid Leukemia, Chronic, Chronic Phase

Keywords

Leukemia; Myeloid; Chronic; Chronic-Phase; CML

Outcome Measures

Primary Outcomes (1)

• 5-year event free survival

  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.

  ongoing throughout study (5 years)

Study Arms (2)

Arm A - Imatinib

ACTIVE COMPARATOR

Imatinib 400mg daily

Drug: Imatinib

Arm B - Dasatinib

EXPERIMENTAL

Dasatinib 100mg daily

Drug: Dasatinib

Interventions

Imatinib DRUG

Oral Imatinib 100mg daily

Also known as: Gleevec/Gleevic

Arm A - Imatinib

Dasatinib DRUG

Oral Dasatinib 100mg daily

Also known as: Sprycel

Arm B - Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• x 109/L platelets or greater
• no evidence of extramedullary leukaemic involvement, with the exception of the hepatosplenomegaly.
• Written voluntary informed consent.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (1)

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• Neelakantan P, Gerrard G, Lucas C, Milojkovic D, May P, Wang L, Paliompeis C, Bua M, Reid A, Rezvani K, O'Brien S, Clark R, Goldman J, Marin D. Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies. Blood. 2013 Apr 4;121(14):2739-42. doi: 10.1182/blood-2012-11-466037. Epub 2013 Feb 4.

  PMID: 23380743 DERIVED

• Marin D, Hedgley C, Clark RE, Apperley J, Foroni L, Milojkovic D, Pocock C, Goldman JM, O'Brien S. Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib. Blood. 2012 Jul 12;120(2):291-4. doi: 10.1182/blood-2012-01-407486. Epub 2012 May 29.

  PMID: 22645182 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia; Bronchiolitis Obliterans Syndrome

Interventions

Imatinib Mesylate; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2010
• First Posted: October 27, 2011
• Study Start: August 1, 2008
• Primary Completion: March 7, 2018
• Study Completion: March 7, 2018
• Last Updated: April 24, 2018

Record last verified: 2018-04

Locations

GB (1)