| 6 | |
| RBR-5hzmjx | |
| A Phase II Study of Dasatinib Therapy in Children and Adolescents with Ph+ Leukemia
with Resistance or Intolerance to Imatinib | |
| A Phase II Study of Dasatinib Therapy in Children and Adolescents with Ph+ Leukemia
with Resistance or Intolerance to Imatinib | |
| None | |
| recruiting | |
| Intervention | |
| 2, randomized-controlled, open | |
| 2 | |
| None | |
| None | |
| None | |
| 2011-06-27 | |
| 2010-03-01 | |
| None | |
| None | |
| https://ensaiosclinicos.gov.br/rg/RBR-5hzmjx | |
| None | |
| Written informed consent from subject, or from parents or legal guardians for
minor subjects, according to local law and regulation.
Cohort #1: Subjects must have Ph+ CML in CP which is defined by the
presence of all the following criteria:
< 15% blasts in peripheral blood and bone marrow
< 20% basophils in peripheral blood
< 30% blasts + promyelocytes in peripheral blood and bone marrow
>= 100 X 109 platelets/L unless thrombocytopenia secondary to recent
treatment
No extramedullary involvement other than liver or spleen
Ph+ or variant must be demonstrated by bone marrow cytogenetics
Cohort #2: Subjects must have Ph+ ALL or Ph+ AP- or BP-CML:
Ph+ ALL have to be in first or subsequent relapse [ >= 25% blasts in bone
marrow] or fail to achieve remission after imatinib
AP-CML must meet at least one of the following criteria:
>= 15% but < 30% blasts in peripheral blood or bone marrow
>= 30% blasts + promyelocytes in peripheral blood and in bone marrow
(but percent alone has to be < 30%)
>= 20% basophils in peripheral blood or bone marrow
< 10 X 109/L platelets unrelated to therapy
BP-CML has to meet all the following criteria:
>= 30% blasts in peripheral blood or bone marrow
Presence of extramedullary blastic disease other than lymph nodes,
liver or spleen
Subjects have to be proven resistant or intolerant to imatinib:
For both cohorts, intolerance to imatinib is defined as the occurrence of any
toxicity grade >= 3 considered at least possibly related to imatinib and that led
to discontinuation of previous imatinib therapy.
For Cohort #1, resistance to imatinib must meet at least one of the following
criteria:
Failure to achieve, or loss of, CHR after >= 3 months of imatinib at a
daily dose of 260 mg/m2 or greater;
Failure to achieve MCyR after >=6 months or CCyR after >= 12 months of imatinib therapy at a daily dose of 260 mg/m2 or greater;
Absolute increase of >= 30% of the percentage of Ph+ metaphases,
confirmed at >= 6 week interval, after prior MCyR to imatinib at a daily
dose of 260 mg/m2 or greater.
For Cohort #2, resistance to imatinib must meet at least one of the following
criteria:
Failure to achieve CHR while on imatinib after a >= 4-week treatment
or a >= 50% increase in peripheral blood blasts over a 2-week period
Subjects who achieved a CHR subsequently no longer meet the criteria
consistently over a consecutive 2-week period while receiving imatinib
Absolute increase of >= 30% of the percentage of Ph+ metaphases,
confirmed at >= 6 week interval, after prior MCyR to imatinib.
Lansky or Karnofsky scale > 50
Life expectancy >= 12 weeks
Subjects must have recovered to baseline or Grade 1 (NCI CTCAE, version 3.0)
from the toxicities (except alopecia) resulting from recent therapies, including
chemotherapy, hormonal therapy, immunotherapy, biological therapy or
investigational product and radiation therapy.
Serum Na, K, NaHC03, Mg, P and Ca levels within institutional normal limits
and AST, ALT, bilirubin, BUN or urea, creatinine ? Grade 2 (NCI CTCAE,
Version 3.0).
Men and women, age >= 1 to < 21 years.
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after
the last dose of investigational product in such a manner that the risk of pregnancy
is minimized.
WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation,
or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined
as:
• Amenorrhea >= 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement
therapy [HRT], a documented serum follicle stimulating hormone [FSH] level
> 35 mIU/mL)
Women who are using oral contraceptives, other hormonal contraceptives
(vaginal products, skin patches, or implanted or injectable products), or
mechanical products such as an intrauterine device or barrier methods
(diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing
abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
WOCBP 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. | |
| WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 12 weeks after the last dose of
investigational product.
Women who are pregnant or breastfeeding
Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
Sexually active fertile men not using effective birth control if their partners are WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 4 weeks after the last dose of
investigational product.
Subjects for whom potentially-curative therapy is available, including
hematopoietic stem-cell transplantation (HSCT) at the time when subject is
assessed for enrollment
Subjects with isolated central nervous system disease are excluded from study.
This criterion relates to subjects with CNS-3 disease (? 5 leukemic blasts per
cubic millimeter in a sample with < 10 erythrocytes per cubic millimeter).
Subjects with CNS-1 (no detectable blast cells in a sample of cerebrospinal fluid)
and CNS-2 (< 5 leukemic blast cells in a sample with < 10 erythrocytes per cubic
millimeter) are eligible for study. Subjects with a combined relapse which also
involves the CNS are eligible, provided this is asymptomatic (no convulsions or
other neurological symptoms).
Isolated extramedullary disease, with < 5% blasts in bone marrow
Any serious uncontrolled medical disorder that would impair the ability of the subject to receive protocol therapy, including:
Ongoing uncontrolled infection
Clinically-significant disorder of platelet function (e.g. von Willebrand’s
disease) or ongoing gastrointestinal bleeding
Clinically-significant cardiovascular disease, congenital long QT syndrome,
history of ventricular arrhythmias or heart block, or prolonged QTc interval >
450 ms (Fridericia correction) on baseline electrocardiogram
Subjects diagnosed with the T315I mutation (mutation testing should be
performed according to the investigator’s standard practice and is not
mandatory at sites without BCR-ABL testing available).
Subjects who have experienced hypersensitivity to dasatinib or to any of the excipients. Inactive ingredients in dasatinib tablets include: lactose
monohydrate, microcrystalline cellulose, croscarmellose sodium,hydroxypropyl cellulose, and magnesium stearate. The tablet coating consists of hypromellose, titanium dioxide, and polyethylene glycol.
Subjects with hereditary problems of galactose intolerance or Lapp lactase
deficiency or glucose-galactose malabsorption.
Expected non-compliance to protocol schedule or unable to have regular followup
due to psychological, social, familial or geographic reasons
Prior therapy with dasatinib.
Any investigational agent or any other anti-cancer agent within 14 days prior to
treatment start. Imatinib mesylate may be continued up to 7 days before treatment
start, or, in the presence of rising peripheral blast cells, imatinib may be continued up to 2 days before treatment start. If required for control of peripheral blast cells,hydroxyurea, corticosteroids, 6-mercaptopurine or 6-thioguanine may be given up
to 2 days before treatment start.
Subjects requiring ongoing medications which may:
Have a known risk of causing QTc prolongation ii) Irreversibly inhibit platelet function, or anticoagulants (Does not apply to low-dose heparin for prophylaxis or to heparin flushes for i.v. lines)
For Cohort #3: Prior chemotherapy, immunotherapy, or radiotherapy for CML
with the exception of hydroxyurea.
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness | |
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| 2026-05-11 05:16:35 | |