CA180-363

perttu.koskenvesa - 18.01.2012 - 23:45

Tutkimuksen nimi, lupapäivämäärät, vastuututkija, keskukset

An Open-Label, Randomized, Multicenter Phase 2 Trial of Dasatinib (Sprycel ®) vs Dasatinib plus Smoothened Antagonist (BMS- 833923) in the Treatment of Subjects with Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML

Eettisen tmk:n/Fimean lupapäivämäärät:

Toimeksiantaja: BMS

Tutkimuksen vaihe: Faasi II

Tutkimuksen vastuuhenkilö: Kimmo Porkka

Osallistuvat keskukset (vastuututkijat): HUS (Kimmo Porkka)

Lyhyt yhteenveto

  • Primary Objective: SMO-inhibiittoria ei voitu aloittaa potilaille, nyt yhden haaran dasatinibitutkimus
  • Secondary Objectives

Sisäänottoaiheet

1) Target Population

a) Confirmed prior diagnosis of chronic myeloid leukemia (CML) or Ph+ALL

b) Evidence of disease, classified as

i) Chronic-phase CML (CML-CP), with cytogenetically-documented Ph+ cells on BMA ≤ 6 weeks prior to treatment start

(1) must have all of the following

(a) < 15% blasts in peripheral blood and BMA

(b) < 30% blasts + promyelocytes in blood and BMA

(c) < 20% basophils in blood and BM

(d) ≥ 100 x 109/L platelets (unless related to treatment), and

(e) no extramedullary disease other than hepatosplenomegaly

 

3) Signed Written Informed Consent

4) Age and Reproductive Status

a) Subjects ≥ 18 years of age.

b) Women of childbearing potential (WOCBP; see Section 3.3.3 for definition) must use an acceptable method of contraception to avoid pregnancy throughout the study, for at least 1 month after the last dose of dasatinib and at least 3 months after the last dose of BMS-833923 in order that the risk of pregnancy is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of βHCG) within 72 hours prior to the start of investigational product

 

Poissulkuaiheet

1) Target Disease Exceptions

2) Medical History and Concurrent Diseases

a) Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy, including

i) Pleural or pericardial effusion of Grade ≥ 2 in previous 12 months

ii) Clinically-significant gastrointestinal disease (eg, uncontrolled nausea or malabsorption syndrome) that would compromise absorption of study drug

iii) Thromboembolic disease requiring ongoing anticoagulation

iv) Clinically-significant coagulation or platelet function disorder (other than related to thrombocytopenia), eg, von Willebrand’s disease

v) Other active malignancy requiring concurrent intervention

b) Uncontrolled or significant cardiovascular disease, including any of the following:

i) Myocardial infarction, uncontrolled angina or congestive heart failure within 6 months prior to study entry

ii) Left ventricular ejection fraction (LVEF) <45%

iii) Significant cardiac conduction abnormality, including

(1) History of clinically-significant ventricular arrhythmia

(2) History of second or third degree heart block or diagnosed congenital long QT syndrome (unless a pacemaker has been implanted)

(3) Prolonged QTcF interval ≥ 450 msec on baseline ECG

 

3) Physical and Laboratory Test Findings

a) Grade ≥ 3 peripheral blood counts (only applies to CML-CP), ie.:

i) ANC < 1,000 cells/mm3

ii) Platelet count < 50,000 cells/mm3

iii) Hemoglobin < 8 g/dL (transfusion-support permitted)

b) Laboratory abnormalities (per CTCAE v 3.0):

i) Serum calcium (corrected for albumin) or phosphate below ILLN (Institutional lower limit of normal; eligible if repleted by supplementation)

ii) Baseline Mg and amylase or lipase Grade ≥ 1

iii) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 X IULN. Total bilirubin > 1.5 X institutional upper limit of normal (IULN; unless Gilbert syndrome has been diagnosed)

iv) Reduced renal function, defined as serum creatinine > 3 X IULN

v) Other chemistry abnormalities Grade ≥ 2

 

4) Allergies and Adverse Drug Reaction

a) History of allergy to dasatinib or compounds chemically related to BMS-833923

5) Sex and Reproductive Status

a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) before and for at least 3 months after the last dose of study medication.

b) Women who are pregnant or breastfeeding.

c) Women with a positive pregnancy test at enrollment or prior to administration of study medication.

 

6) Prohibited Treatments and/or Therapies

 

c) Concomitant use of medications known to have a risk of causing “Torsades de Pointes” (Section 3.4.1.2)

d) Concomitant use of strong inhibitors of the CYP3A4 isoenzyme (Section 3.4.1.3)

 

7) Other Exclusion Criteria

a) Dementia or serious psychiatric condition that may compromise the informed consent process and increase the risks associated with study participation

b) Prisoners or subjects who are involuntarily incarcerated

c) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Viimeksi muokannut: 
Lauri Mäkinen - 27.05.2015 - 18:14