Study title
BOSTRO = CML Treated With Bosutinib After Relapse
Scientific title
Single Nucleotide Polymorphism Association With Response and Toxic Effects in Patients With Ph+ CP-CML Treated With Bosutinib After Relapse to Previous Treatment (NCT02445742, EudraCT 2013-004323-372013-004323-37)
Indication and most important inclusion criteria
This study includes patients who:
- have Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase (CP-CML)
- have not responded optimally to previous treatment with imatinib, nilotinib or dasatinib, defined as BCR-ABL above 10% at 3 months after starting treatment
- are at least 18 years old
- have recovered from any adverse effects of previous treatments, except for hair loss
- have an Eastern Co-Operative Group (ECOG) status of 0 or 1
- have adequate bone marrow, kidney and liver function
Short description of intervention
This study investigates whether specific features (so called single nucleotide polymorphisms) in genes are related to the activity and adverse effects of bosutinib. The study also evaluates the safety and efficacy of bosutinib in patients after relapse or intolerance to previous tyrosine kinase inhibitors (TKIs).
Patients who have not responded optimally to previous TKI treatment will receive bosutinib 500 mg per day for 2 years, until the disease progresses, unacceptable side effects occur or the patient withdraws consent to participate
Type of study
Second line trial after treatment failure
Current status
Recruiting
Study sponsor
Fundación PETHEMA para el tratamiento de la leucemia y el linfoma, Spain, with financial support from Pfizer, S.L.U.
Scientific lead / contact
Dr Luis Felipe Casado
PETHEMA
Principal investigator
Dr Luis Felipe Casado
PETHEMA
Additional information
Study description in the US register ClinicalTrials.gov,, a service of the U. S. National Institutes of Health
Study centers / principal investigators
Spain
Gran Canaria
C. H. U. de Gran Canaria Dr. Negrín
Dr. Maite Gómez Casares
Madrid
C. H. Gregorio Marañón
Dr. Santiago Osorio
Madrid
C. U. La Paz - H. U. La Paz
Dr. Raquel de Paz
Madrid
H. Ramón y Cajal
Dr. J. Valentín García Gutiérrez
Madrid
H. U. de la Princesa
Dr. Juan Luis Steegmann
Madrid
H. U. Fundación Jiménez Díaz
Dr. José Luis López Lorenzo
Madrid
Hospital Universitario 12 de Octubre
Dr. Joaquin Martinez
Málaga
C. H. Regional de Málaga , H. General
Dr. Antonio Jiménez Velasco
Palma de Mallorca
H. U. Son Espases
Dr. Andrés Novo
Salamanca
C. Asistencial U. de Salamanca
Dr. Fermín Sánchez Guijo
Santiago de Compostela
C. H. U. de Santiago
Dr. Manuel Pérez Encinas
Toledo
H. Virgen de la Salud
Dr. Luis Felipe Casado
Zaragoza
Clínica Quirón Zaragoza S.A.
Dr. Pilar Giraldo
Chronic Myeloid Leukemia
also called: Chronic Myelogeneous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
Philadelphia chromosome
A certain change in chromosomes (on chromosome 22) found in 95% of patients who have CML. The Philadelphia chromosome results from a mutation that involves the fusion of parts of chromosome 9 and chromosome 22 (the bcr-abl fusion gene)
Inclusion criteria
Inlusion criteria define which subjects may participate in a clinical study. Study subjects must fulfill all inclusion criteria (e.g. with regard to sex, age, previous diseases). This ensures a uniform composition of the study population and minimizes the risk of influences that distort the study results.
Chronic phase
The earliest phase of CML development.
Side effect
Adverse effects of a treatment:, side effects limit the maximum tolerable dose in particular during chemotherapy.
Chromosome
A chromosome is a structure of DNA that carries the genetic makeup in the nucleus of the cell. Chromosomes contain giant chain molecules of DNA, coiled and folded as aggregates with specific proteins. Chromosomes ensure that during cell division the hereditary information is evenly distributed to the daughter cells. Normal human body cells have 46 chromosomes. Cancer cells can have a different number and/or structure of chromosomes.
Indication
In medicine, a reason to use a certain diagnostic test, therapeutic procedure or medication. The opposite of indication is contraindication.
Bosutinib
Bosutinib (development name SKI-606, trade name Bosulif), a second generation tyrosine kinase inhibitor.
Also called Bosulif|SKI-606|SKI606
Dasatinib
Trade name: Sprycel, development name: BMS-354825, inhibits BCR-ABL and SRC tyrosine kinases. Authorized for marketing in the EU since 2006 for the treatment of CML and Ph+ALL.
Other names: BMS-354825|BMS354825|Sprycel
Nilotinib
Trade name: Tasigna, development name: AMN107, inhibits BCR-ABL tyrosine kinase. Authorized for marketing in the EU since 2007 for the treatment of CML and Ph+ALL.
Other names: |AMN107|Tasigna
Imatinib
Imatinib, trade name Glivec/Gleevec, development name STI-571, a first-generation BCR-ABL tyrosine kinase inhibition. Authorized for marketing since 2002 for the treatment of CML and Ph-positive ALL.
Other names: Gleevec|Glivec
BCR-ABL
The abnormal gene that characterizes Chronic Myeloid Leukemia, which is a fusion of the BCR gene of chromosome 9 and the ABL gene of chromosome 22
Chronic
Long-lasting, slowly developping
TKIs
Tyrosine Kinase Inhibitors, a class of drugs that block an enzyme involved in the mechanism of division of cells
ECOG
Eastern Cooperative Oncology Group Index to classify the quality of life of cancer patients on a scale ranging from 0 (fully active, able to carry on all predisease activities without restriction) to 5 (death).
Also often referred to as ECOG performance status.
Gene
A unit of information present as DNA; a gene usually contains the blueprint for a protein.
CML
Chronic Myeloid Leukemia, also called Chronic Myelogenous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
Ph+
Abbreviation for "Philadelphia-Chromosome-positive", meaning the presence of a certain change in chromosomes (on chromosome 22) found in 95% of patients who have CML. The Philadelphia chromosome results from a mutation that involves the fusion of parts of chromosome 9 and chromosome 22 (the bcr-abl fusion gene).
CHR
Abbreviation for Complete Hematologic Response. The blood cell count has returned to normal, and tests don’t show any immature white blood cells. Also, the spleen has returned to a normal size if it was enlarged.
