dasatinib in chronic phase chronic mieloid leukemia patients with chronic toxicity to imatinib

Phase 1

• Conditions: CP-CML patients with non hematologic low toxicity grade to imatinib; MedDRA version: 16.1Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-006180-21-DE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-23
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

- signed Informed
- Subjects with CP-CML achieving an optimal response (either CHR by 3 months,
PCyR by 6 months, or CCyR by 12 months) to imatinib = 400 mg/day treatment
- Currently experiencing at least one imatinib-related Grade 1 or 2 non-hematologic
adverse event persisting for at least 2 months or recurring at least 3 times in the
preceding 12 months, despite best supportive care
Daily ECOG performance status = 0 – 2
- Life expectancy >6 months
- Adequate renal function defined as serum creatinine = 3 times the institutional
ULN
- Adequate hepatic function defined as: total bilirubin = 3.0 times the institutional
ULN; alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) = 5.0 times the institutional upper limit of normal (ULN)
- Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or
equal to the institutional lower limit of normal. Subjects with low K, Mg levels,
total serum Ca and/or ionized Ca must be repleted to allow for protocol entry.
- Men and women, ages 18 or older
- Women of childbearing potential (WOCBP) must use highly effective methods of
birth control to minimize the risk of pregnancy. WOCBP must follow instructions
for birth control for the entire duration of the study including a minimum of 1
month (4 weeks) after dosing has been completed.
Acceptable methods of highly effective birth control include:
• Condom with spermicide
• Diaphragm and spermicide
• Cervical cap and spermicide
The use of intrauterine devices, (IUDs) shall be at the discretion of the
investigator.
Women must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the
start of investigational product.
- Women must not be breastfeeding
- Sexually active fertile men must use highly effective birth control if their partners
are WOCBP. Men that are sexually active with WOCBP must follow instructions
for birth control for the entire duration of the study and a minimum of 1 month
(4 weeks) after dosing has been completed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

- Previous treatment with any other TKI, except imatinib
- Current Grade 3 or 4 imatinib-related adverse event
- Subjects with clonal evolution in Ph+ cells observed in = 2 metaphases at baseline
bone marrow (BM) cytogenetic test, unless the same abnormalities were present
at diagnosis (See Section 5.8.2 for subjects exempt from baseline bone marrow
cytogenetic assessment)
- Subjects with previous loss of CHR or loss of major cytogenetic response
(MCyR) on imatinib
- Previous diagnosis of accelerated or blast phase CML
- A serious uncontrolled medical disorder or active infection that would impair the
ability of the subject to receive protocol therapy
- Uncontrolled or significant cardiovascular disease, including any of the following:
i. Congestive cardiac failure (NYHA > 2) within 3 months
ii. Diagnosed or suspected congenital long QT syndrome
iii. Any history of clinically significant ventricular arrhythmias
iv. Prolonged QTcF interval on pre-entry electrocardiogram (> 450 msec)
v. Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
vi. Uncontrolled angina within 3 months
vii. Prior myocardial infarction within 6 months
viii. Uncontrolled hypertension
- Known pulmonary arterial hypertension
- Pleural or pericardial effusions of any grade at study entry are excluded. Subjects
previously diagnosed with pleural/pericardial effusion of any grade resolved at the
time of study entry are allowed
- History of significant bleeding disorder unrelated to CML, including
i. Diagnosed congenital bleeding disorders (eg, von Willebrand’s disease)
ii. Diagnosed acquired bleeding disorder within one year (eg, acquired antifactor
VIII antibodies)
- Serious mental illness interfering with the ability to participate in the study
- Prior documented T315I mutation (Enrollment is not dependent upon results of
baseline mutation analysis)
- Patients who are pregnant or breastfeeding or likely to become pregnant
- Men whose partner is unwilling or unable to avoid pregnancy
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.
- Subjects unable to complete patient-reported outcomes without assistance

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified