Chronic lymphocytic leukemia MedDRA version: 14.1 Level: LLT Classification code 10008978 Term: Chronic lymphocytic leukemia refractory System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10008977 Term: Chronic lymphocytic leukemia recurrent System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: dexamethasone
CAS Number: 50022
Concentrat
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - B-CLL confirmed according to WHO Classification; - Fludarabine refractory, defined as no response or relapse within 12 months after the last administration of fludarabine monotherapy or fludarabine containing regimen, and needing treatment, or Refractory or relapsed and needing treatment and having deletion of 17p13, or Refractory or relapsed within 24 months after the last administration of fludarabine combined with a monoclonal antibody and needing treatment; - Age 18-70 years inclusive; - WHO performance status = 2 (see appendix E); - HCT-CI = 2 (see appendix F); - Written informed consent. 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 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: - Intolerance to exogenous protein administration - Previously treated with DHAP - Richter’s transformation; - Suspected or documented CNS involvement by CLL; - Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease); - Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D); - Severe neurological or psychiatric disease; - Significant hepatic dysfunction (serum bilirubin or transaminases = 3 times upper limit of normal) except when caused by leukemic infiltration; - Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration); - History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma; - Active, uncontrolled infections; - Patient known to be HIV-positive; - Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess, on an intention-to-treat basis, the efficacy and safety of a treatment protocol including salvage chemoimmunotherapy (R-DHAP) followed, in the absence of progression, by RIC alloSCT from sibling or unrelated donors, in high-risk CLL patients as measured by the progression free survival ;Secondary Objective: - To assess the safety and toxicity of three courses of R-DHAP - To assess the response to three courses of R-DHAP. - To assess PFS and OS after alloSCT. - To asses PFS and OS after maximally 6 R-DHAP in case no alloSCT was performed - To assess disease status at two years after SCT. - To assess the incidence and course of MRD in patients with CR - To assess overall survival from registration. - To assess the incidence of complete, partial and no engraftment. - To evaluate the incidence and severity of acute and chronic GVHD, and of other treatment related toxicity; - To evaluate the response of progressive disease or increasing MRD to lowering of immunosuppression or DLI. - To assess the time to next treatment excluding MRD triggered lowering of immunosuppression or DLI. - To assess the prognostic value of risk factors at entry including IgH mutation status and karyotypic abnormalities with respect to PFS. ;Primary end point(s): progression-free survival from registration with progression defined as time to: a. death due to any cause, or b. progression or relapse excluding progressive MRD triggering cessation of immunosuppression or DLI whichever comes first ;Timepoint(s) of evaluation of this end point: On Study, after 3 R-DHAP cycles, after 3 mnths SCT (until 24 mnths), in case no donor after last R-DHAP cycle (max 6 cycles), follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • incidence and severity of tumor lysis during first course of R-DHAP • response to three courses of R-DHAP including SD; • percentage of successful donor searches, • percentage of patients who received alloSCT • best response on protocol • engraftment after alloSCT; • incidence and severity of acute and chronic GVHD; • toxicity; • overall survival (OS) from registration; • response of MRD to immunomodulation (either accelerated cessation of immunosuppression or DLI) • response of PD to recommended off-protocol immunomodulation (either accelerated cessation of immunosuppression or DLI) • disease status at two years after registration; • PFS and OS after alloSCT ;Timepoint(s) of evaluation of this end point: On Study, after 3 R-DHAP cycles, after 3 mnths SCT (until 24 mnths), in case no donor after last R-DHAP cycle (max 6 cycles), follow-up | — |
Countries
Belgium, Netherlands
Contacts
Public ContactHDC
HOVON
Outcome results
None listed