Dasatinib Combination for Chronic Lymphocytic Leukemia(CLL) With Refractory Disease
D'ACCORD
1 other identifier
interventional
35
1 country
4
Brief Summary
Patients with chemo refractory CLL have a poor prognosis. 2 independent mechanisms are attributed to the development of chemoresistance in CLL. The first is a shift in the balance between pro- and anti-apoptotic regulators. The second mechanism is based on acquired mutations resulting in a dysfunctional p53 response. Recent studies indicate that the tyrosine kinase inhibitor dasatinib acts synergistically with both purine analogies and alkylating agents. Also, dasatinib has the potency to restore the apoptotic balance of CLL cells. Hypothesis: Dasatinib will be clinically active in chemo-refractory CLL patients and will act synergistically with the purine-analogue fludarabine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2008
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2008
CompletedFirst Submitted
Initial submission to the registry
January 15, 2010
CompletedFirst Posted
Study publicly available on registry
January 18, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedAugust 31, 2011
August 1, 2011
4.3 years
January 15, 2010
August 29, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
response rate and response quality
At 32 weeks of either dasatinib monotherapy or after 6 cycles of fludarabine and dasatinib combination
Secondary Outcomes (1)
overall safety profile of these treatment approaches, event free survival, progression free survival, relapse or death, disease free survival
3 years
Study Arms (1)
Dasatinib
EXPERIMENTALPatients will be treated with dasatinib monotherapy 100mg daily. At four weeks patients will be re-evaluated. Patients with less than a partial response will receive fludarabine (orally 40mg/daily for 3 days q28) in addition to dasatinib.
Interventions
Chemo-refractory CLL patients will be treated with dasatinib monotherapy 100mg daily.Patients with less than a partial response at 4 weeks will receive fludarabine (orally 40mg/daily for 3 days q28) in addition to dasatinib for a maximum of 6 cycles. Patients with at least a partial response will continue dasatinib monotherapy. Patients that receive monotherapy after the initial 28 days and that develop progressive disease will 'cross-over' to the combination treatment.
Eligibility Criteria
You may qualify if:
- CLL confirmed according to the IWCLL Working Group criteria;
- Binet stages A or B with indication for treatment according to IWCLL guidelines, Binet C AND
- Fludarabine refractory, defined as relapse (any sign of disease recurrence or progression with or without indication for treatment ≤ 6 months following fludarabine containing chemo(immuno)therapy;
- Age 18-80 years inclusive;
- WHO performance status ≤ 2;
- No possibility for rapid reduced intensity allogeneic hematopoietic stem cell transplantation;
- At least 4 weeks without any treatment before study entry;
- Negative pregnancy test;
- Written informed consent;
You may not qualify if:
- Richter's transformation;
- Suspected or documented CNS involvement by CLL;
- Grade 3 cytopenia not due to bone marrow infiltration
- Concurrent medical condition which may increase the risk of toxicity, including:
- Pleural or pericardial effusion of any grade
- Cardiac Symptoms, including:
- Uncontrolled angina, congestive heart failure or MI within (6 months)
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration;
- Severe pulmonary dysfunction (CTCAE grade III-IV);
- Active hepatitis B infection;
- History of significant bleeding disorder unrelated to the CLL, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Maastricht university medical center
Maastricht, Limburg, 6229 HX, Netherlands
Academic Medical Center
Amsterdam, North Holland, 1105 AZ, Netherlands
University Medical Center Groningen
Groningen, Provincie Groningen, 9713 GZ, Netherlands
Erasmus MC-Daniel den Hoed Cancer Center
Rotterdam, South Holland, 3015 CE, Netherlands
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Arnon P kater, MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- PRINCIPAL INVESTIGATOR
Marinus HJ van Oers, MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- A.P. Kater, MD, PhD
Study Record Dates
First Submitted
January 15, 2010
First Posted
January 18, 2010
Study Start
October 1, 2008
Primary Completion
January 1, 2013
Study Completion
January 1, 2016
Last Updated
August 31, 2011
Record last verified: 2011-08