NCT00895297TerminatedPhase 2
Phase II Efficacy and Safety Study of Dasatinib in Patients With Chronic and Accelerated Phase Chronic Myeloid Leukemia Relapsing After Allogeneic Blood or Bone Marrow Transplantation
European Society for Blood and Marrow Transplantation9 sites in 4 countries50 target enrollmentStarted: February 1, 2010Last updated:
Conditions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 50
- Locations
- 9
- Primary Endpoint
- CMR as determined by two consecutive (-) RT-PCR tests for the presence of BCR-ABL transcripts in peripheral blood samples 1 year after starting Dasatinib therapy. The expected CMR of >30% would be regarded as being clinically relevant
Study Overview
Brief Summary
This is a phase II efficacy (indicates the capacity for beneficial change or therapeutic effect) and safety study of Dasatinib in patients with relapsed Chronic Myeloid Leukemia (CML) following a Stem Cell Transplant (SCT) and who are not benefiting from other treatment, such as imatinib therapy.
A relapse is when an illness that has seemed to be getting better, or to have been cured, comes back or gets worse again.
A total of 50 patients ≥18 years of age will be registered on the trial.
Detailed Description
Primary Objective:
- To assess the efficacy of Dasatinib therapy in chronic and accelerated phase BCR-ABL (+) (Ph + and Ph -) CML patients that undergo molecular, cytogenetic or haematological relapse following SCT.
Secondary Objective(s):
- To assess the impact of Dasatinib therapy on patient survival after relapse post-SCT and the incidence of any subsequent need for 'rescue' DLI.
- To assess the safety of Dasatinib in this clinical context using this specific dose regimen
Chronic myeloid leukaemia (CML) is a form of cancer that starts in cells within the bone marrow called haematopoietic stem cells. Stem cells are immature cells which can divide many times and eventually produce all the lymphocytes and myeloid cells present in the blood. They are produced in the bone marrow - the spongy tissue found in large bones, including the pelvis, sternum, limb bones and the ribs.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female patients greater or equal to 18 years of age.
- •Diagnosed with BCR-ABL (+) Chronic Myeloid Leukemia (they can be Philadelphia chromosome positive or negative)
- •Prior therapy including imatinib
- •Patients transplanted from an HLA-identical sibling or an HLA-matched unrelated donor.
- •Patients transplanted in first chronic phase or accelerated phase.
- •Patients with untreated relapse of BCR-ABL (+) CML (they can be Philadelphia chromosome positive or negative) after allogeneic transplantation and entered within 6 weeks of the first detection of relapse.
- •Molecular, cytogenetic or haematological relapse in chronic or accelerated phase.
- •Written informed consent.
- •Absence of serious concomitant illness
Exclusion Criteria
- •Patients relapsing in blast crisis.
- •Patients transplanted after blastic transformation of CML.
- •Patients receiving any therapy for relapse other than withdrawal of immunosuppression (DLI is not permitted).
- •Patients treated with other investigational agents during the previous 30 days
- •Patients previously treated with Dasatinib.
- •Absence of written informed consent.
- •Presence of serious concomitant disease.
- •History of a significant bleeding disorder unrelated to CML.
- •Pregnancy or lactation status positive.
- •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.
- •Total serum bilirubin level more than 2 x the upper limit of the normal range of the laboratory where the analysis is performed.
- •Serum creatinine concentration more than 1.5 x the upper limit of the normal range of the laboratory where the analysis is performed.
- •Concomitant Medications, any of the following should be considered for exclusion:
- •Category I drugs that are generally accepted to have a risk of causing Torsades de Points including: (Patients must discontinue drug 7 days prior to starting Dasatinib):
- •quinidine, procainamide, disopyramide.
- •amiodarone, sotalol, ibutilide, dofetilide.
- •erythromycin, clarithromycin.
- •chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, ziprasidone.
- •cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
- •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.
Outcomes
Primary Outcomes
CMR as determined by two consecutive (-) RT-PCR tests for the presence of BCR-ABL transcripts in peripheral blood samples 1 year after starting Dasatinib therapy. The expected CMR of >30% would be regarded as being clinically relevant
Time Frame: 4 years
Secondary Outcomes
- Adverse event (AE) rate.(4 years)
- Progression free survival (PFS).(4 years)
- Overall survival (OS) - Limited to 3 years.(4 years)
- Complete cytogenetic response (CCyR) at 6 and 12 months post commencing Dasatinib for those that have relapsed at the cytogenetic level.(4 years)
- Major molecular response (MMR) at 12 months post commencing Dasatinib for all patients.(4 years)
- Proportion of patients requiring DLI during the first 12 months(4 years)
- Complete haematological response (CHR) at 3 months post commencing Dasatinib for those that have relapsed at the haematological level.(4 years)
- Rate of dose reductions, interruptions and discontinuations.(4 years)
Investigators
Study Sites (9)
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