Phase II efficacy and safety study of Dasatinib in Patients with Chronic and Accelerated Phase Chronic Myeloid Leukaemia Relapsing after Allogeneic Blood or Bone Marrow Transplantation - CML DASATINIB

• Conditions: chronic myeloid leukaemia; MedDRA version: 9.1Level: LLTClassification code 10009013Term: Chronic myeloid leukaemia

• Registration Number: EUCTR2008-001361-29-GB
• Lead Sponsor: EBMT (European group for Blood and Marrow Transplantation)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1) Male or female patients minimum 18 years of age

2) Diagnosed with BCR-ABL (+) Chronic Myeloid Leukemia (they can be Philadelphia chromosome positive or negative)

3) Prior therapy including imatinib

4) Patients transplanted from an HLA-identical sibling or an HLA-matched unrelated donor.

5) Patients transplanted in first chronic phase or accelerated phase.

6) Patients with untreated relapse of BCR-ABL (+) CML after allogeneic transplantation and entered within 6 weeks of the first detection of relapse.

7) Molecular, cytogenetic or haematological relapse in chronic or accelerated phase.

8) Written informed consent.

9) Absence of serious concomitant illness.

10) Negative pregnancy test for women of child bearing age

11) The need to be affiliated with (NATIONAL) health insurance or beneficiary of such regime
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Patients relapsing in blast crisis.

2) Patients transplanted after blastic transformation of CML.

3) Patients receiving any therapy for relapse other than withdrawal of immunosuppression (DLI is not permitted).

4) Patients treated with other investigational agents during the previous 30 days (list of prohibited therapies can be found in section 8.6.1).

5) Patients previously treated with Dasatinib.

6) Absence of written informed consent.

7)Patients incapable of giving consent personally.

8) Presence of serious concomitant disease.

9) History of a significant bleeding disorder unrelated to CML.

10) Pregnancy or lactation status positive.

11) Patients and/or female partners of male patients not using highly effective method of birth control i.e. intrauterine device (IUD), hormonal (oral pill, injection, implants), tubal ligation or partner’s vasectomy.

12)SGOT and SGPT more than 2.5 x the upper limit of the normal range as determined by the laboratory where the analysis is performed.

13) Total serum bilirubin level more than 2 x the upper limit of the normal range of the laboratory where the analysis is performed.

14) Serum creatinine concentration more than 1.5 x the upper limit of the normal range of the laboratory where the analysis is performed.

15)Concomitant Medications, any of the following should be considered for exclusion:
a)Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting Dasatinib):
i)quinidine, procainamide, disopyramide.
ii)amiodarone, sotalol, ibutilide, dofetilide.
iii)erythromycin, clarithromycin.
iv)chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, zyprasidone.
v)cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
b)The concomitant use of H2 blockers or proton pump inhibitors with Dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving Dasatinib therapy. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of Dasatinib.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of Dasatinib therapy in chronic and accelerated phase BCR-ABL (+) CML patients that undergo molecular, cytogenetic or haematological relapse following SCT.;Secondary Objective: To assess the impact of Dasatinib therapy on patient survival after relapse post-SCT and the incidence of any subsequent need for ‘rescue’ donor lymphocyte infusion (DLI). DLI is currently the gold standard for the treatment of relapse following SCT and involves the infusion of lymphocytes from the transplant donor into the recipient.<br><br>To assess the safety of Dasatinib in this clinical context using this specific dose regimen<br>;Primary end point(s): Complete Molecular Remission as determined by two consecutive negative RT-PCR tests for the presence of BCR-ABL transcripts in peripheral blood samples 12 months after commencing Dasatinib therapy.