Dasatinib Combination for Chronic Lymphocytic Leukemia(CLL) With Refractory Disease (D'ACCORD)
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dasatinib Combination for Chronic Lymphocytic Leukemia Patients With Chemo Refractory Disease|
- response rate and response quality [ Time Frame: At 32 weeks of either dasatinib monotherapy or after 6 cycles of fludarabine and dasatinib combination ] [ Designated as safety issue: No ]
- overall safety profile of these treatment approaches, event free survival, progression free survival, relapse or death, disease free survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2008|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Patients 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.
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.
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|Contact: Arnon P Kater, MD, PhDfirstname.lastname@example.org|
|Contact: Marjolein Spiering, Msemail@example.com|
|Maastricht university medical center||Not yet recruiting|
|Maastricht, Limburg, Netherlands, 6229 HX|
|Contact: Michel van Gelder, MD, PhD +31-43 - 387 6543 firstname.lastname@example.org|
|Academic Medical Center||Recruiting|
|Amsterdam, NH, Netherlands, 1105 AZ|
|Contact: Marjolein Spiering, Ms +31-20-5669111 email@example.com|
|Contact: Arnon P Kater, MD, PhD +31-20-5669111 firstname.lastname@example.org|
|Erasmus MC-Daniel den Hoed Cancer Center||Recruiting|
|Rotterdam, ZH, Netherlands, 3015 CE|
|Contact: Jeanette K Doorduijn, MD, PhD +31-10 7040704 email@example.com|
|University Medical Center Groningen||Recruiting|
|Groningen, Netherlands, 9713 GZ|
|Contact: Simon MG Daenen, MD, PhD +31-50 3616161 firstname.lastname@example.org|
|Principal Investigator:||Arnon P kater, MD, PhD||Academic medical Center, Amsterdam, the Netherlands|
|Principal Investigator:||Marinus HJ van Oers, MD, PhD||Academic Medical Center, Amsterdam, the Netherlands|