Phase I study of Src/Abl tyrosine kinase inhibitor dasatinib [BMS-354825] in children and adolescents with relapsed or refractory leukemia, Protocol ITCC 005. Revised protocol #4, incorporating Amendments 01, 02, 03, and 04. - Protocol ITCC 005

• Conditions: Children and adolescents, 1-20 years, with CML or relapsed Philadelphia positive ALL resistant or intolerant to imatinib or second or subsequent relapse of other ALL or AML; MedDRA version: 14.1Level: HLGTClassification code 10024324Term: LeukaemiasSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2005-002882-35-IT
• Lead Sponsor: BRISTOL-M.SQUIBB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-04-21
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Diagnosis (see § 3.2.1 for definitions of resistance and intolerance): Stratum 1: Ph+ chronic myeloid leukemia in chronic phase with resistant or progressive disease during, or intolerance to, imatinib, including: i) failure to achieve, or loss of, complete hematologic response after ≥ 3 months of imatinib ii) failure to achieve major cytogenetic response [minor or equal to 35% Ph+ metaphases] after ≥ 6 months or complete cytogenetic response [0% Ph+ metaphases] after ≥ 12 months of imatinib iii) recurrence of Ph+ clone with ≥ 35% abnormal metaphases after prior major cytogenetic response to imatinib iv) increase in BCR-ABL signal by quantitative PCR of ≥ 1 logs, confirmed at ≥ 6 week interval [must be discussed with Principal Investigator]. [Note: subjects enrolled in Stratum 1 should have an ongoing search for an identical HLA donor while on study]. Stratum 2/3: i) Ph+ advanced phase CML (accelerated phase (AP), myeloid blast phase (MBP), lymphoid blast phase (LBP)) resistant to imatinib; or ii) Relapsed or refractory Ph+ acute lymphoblastic leukemia (Ph+ALL) after imatinib; iii) Ph+ acute myeloid leukemia in second or subsequent relapse [≥ 25% blasts in bone marrow] after prior imatinib. Note: for strata 1 and 2/3 it is not required that imatinib be the most recent treatment. In addition, biopsy-proven isolated extramedullary leukemia, i.e. with negative BM, is permitted for all strata after discussion with Prinicipal Investigator. Stratum 4: Ph-negative acute leukemia, any cytopathologic subtype, in second or subsequent relapse [≥ 25% blasts in bone marrow] or refractory after 2 or more induction regimens and for whom no therapy of greater curative potential is available. Age major or equal to 1 and < 21 years. Lansky or Karnofsky scale > 60 (see Appendix 1). Life expectancy > 3 weeks. Serum Ca2+ levels above institutional lower limit of normal; Na, K, Mg, Phos, AST, ALT, and Bilirubin ≤ Grade 1, and BUN and Creatinine ≤ Grade 2. No organ toxicity ≥ Grade 2 (except alopecia), and recovered from acute toxicity of previous therapy 7. Able to comply with scheduled follow-up at one of the ITCC-leukemia centers involved in this study. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study medication. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized. Written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects for whom potentially-curative therapy is available, including electing immediate stem-cell transplantation 2. Extramedullary leukemia, specifically with a) symptomatic CNS involvement or b) isolated extramedullary disease, with < 5% blasts in marrow 3. Any serious uncontrolled medical disorder that would impair the ability of the subject to receive protocol therapy, including a) Ongoing uncontrolled infection b) Not recovered from acute toxicity of previous therapy c) Clinically-significant disorder of platelet function (e.g. von Willebrand's disease) or ongoing gastrointestinal bleeding d) 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 4. Expected non-compliance or unable to have regular follow-up due to psychological, social, familial or geographic reasons 5. Subjects who have received: a) Any investigational agent or any other anti-cancer agent within 14 days prior to treatment start. Exception: 6-mercaptopurine or 6-thioguanine may be given up to 2 days before entry, if required. For concomitant use of corticosteroids or hydroxyurea, see §6.6. b) Any prior therapy with dasatinib [BMS-354825] 6. Subjects requiring ongoing medications which a) irreversibly inhibit platelet function, or anticoagulants [see §6.4.1]. (Does not apply to low-dose heparin for prophylaxis or to heparin flushes for i.v. lines) b) have a known risk of causing QTc prolongation 7. WOCBP with a positive pregnancy test prior to study drug administration, or who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the study, or who are pregnant or breastfeeding 8. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

Study & Design

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