Advanced previously untreated Chronic Lymphocytic Leukemia
Conditions
Interventions
Patients will be treated with 6 cycles of chlorambucil, rituximab and lenalidomide followed by 6 cycles of lenalidomide monotherapy.
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
P.O. box 5201
3008 AE Rotterdam
Tel: +31 10 7041560
Fax: +31 10 7041028
e-mail: hdc@erasmusmc.nl
Eligibility
Inclusion criteria
Inclusion criteria: 1. Diagnosis of CLL without prior treatment; 2. Patients with symptomatic (according to IWCLL guidelines) stage A or stage B or stage C; 3. Age ≥ 65 years at the time of signing the informed consent form, or age < 65 years and CIRS ≥ 7; 4. Able to adhere to the study visit schedule and other protocol requirements; 5. WHO performance status of ≥ 2; 6. Laboratory test results within these ranges: absolute neutrophil count ≥ 1.0 x 10^9/l, platelet count ≥ 30 x 10^9/l, creatinine clearance ≤ 60 ml/min, total bilirubin ≤ 25 umol/L, AST & ALT ≤ 2 x ULN; 7. Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting lenalidomide; 8. Patients who are willing and capable to use adequate contraception during the therapy (all men, all pre-menopausal women). Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan; 9. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Patients that are unable or unwilling to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan; 2. Intolerance of exogenous protein administration; 3. Hepatitis B Ag positive, Hepatitis C positive and/or HIV positive patients; 4. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP); 5. Active fungal, bacterial, and/or viral infection; 6. Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide); 7. Use of any other experimental drug or therapy within 28 days of baseline; 8. Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs; 9. Any prior use of lenalidomide; 10. Concurrent use of other anti-cancer agents or treatments; 11. Uncontrolled hyperthyroidism or hypothyroidism; 12. Patients with history of idiopathic deep venous thrombus and/or pulmonary embolism within last three years; 13. Neuropathy ≥ grade 2; 14. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin; squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer (TNM stage of T1a or T1b); 15. Current inclusion in other clinical trials; 16. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For part I of the study: Dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended part II dose (RDL) of Chlorambucil when combined with Rituximab and Lenalidomide. For part II of the study: CR+PR rate. | — |
Secondary
| Measure | Time frame |
|---|---|
| For part I of the study: To evaluate toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR) and clinically relevant hematologic toxicity. For part II of the study: 1. To evaluate the efficacy of Lenalidomide monotherapy in patients without progressive disease after 6 cycles of CR2; 2. To evaluate toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR) and clinically relevant hematologic toxicity; 3. To evaluate progression free survival; 4. To evaluate event-free survival; 5. To evaluate overall survival. | — |
Contacts
Public ContactA.P. Kater
Academic Medical Center, Amsterdam Secretariaat Hematologie F4-224 Meibergdreef 9
Outcome results
None listed