Main info

Identifier:

HO109 CLL

Sponsor:

HOVON

Working group party:

CLL

Age:

>= 18

Stage:

1st Line

Echelon:

Level D

Included patients:

63

(of 62)

Active sites:

35

(of 37)

Title:

Efficacy and safety of first-line therapy with chlorambucil, rituximab and lenalidomide (Revlimid®) (CR2) in elderly patients and young frail patients with advanced Chronic Lymphocytic Leukemia (CLL): a phase I/II trial.

Timeline

News

Flow

Details

Phase:

Prospective Phase I/II study

Monitoring Type:

Not any more

Objectives:

Part I
Primary objective:

• To determine the maximum tolerated dose (MTD) and recommended part II dose level (RDL) of Chlorambucil when combined with Rituximab and Lenalidomide in a 28-days schedule. See paragraph 13 for definitions of MTD and RDL

Secondary objectives:
- To evaluate toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR) and clinically relevant hematologic toxicity

Part II
Primary objective:

• To investigate the efficacy of a maximum of 6 cycles of Chlorambucil with Rituximab plus Lenalidomide at the RDL, as determined by the CR+PR rate

Secondary objectives:

• To evaluate the efficacy of Lenalidomide monotherapy in patients without progressive disease after 6 cycles of CR2
• To evaluate toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR) and clinically relevant hematologic toxicity
• To evaluate progression free survival
• To evaluate event-free survival
• To evaluate overall survival

Eligibility

Inclusion Criteria:

Diagnosis of CLL without prior treatment;

• Patients with symptomatic (according to IWCLL guidelines56 ) Binet stage A / Rai stage 0 or Binet stage B or C / Rai I, II, III or IV (appendix A);
• Age 65 - 80 years, inclusive, at the time of signing the informed consent form, or age 18 – 64, inclusive, and CIRS ≥ 7 (appendix E);
• Able to adhere to the study visit schedule and other protocol requirements;
• WHO performance status of ≤ 2;
• 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 μmol/L, AST & ALT ≤ 2 x ULN; in case the estimated creatinine clearance is too low (≥40, <60 ml/min) one may determine the Glomular Filtration Ratio (GFR) from creatinine by 24 hours urine collection. This should be ≥ 60 ml/min ,
• 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;
• Patients who are willing and capable to use adequate contraception during the therapy (all men, all women of childbearing potential). Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan;
• Written informed consent.

Exclusion Criteria:

• Patients that are unable or unwilling to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan;
• Intolerance of exogenous protein administration;
• Hepatitis B Ag positive, Hepatitis C positive and/or HIV positive patients;
• Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP);
• Active fungal, bacterial, and/or viral infection;
• Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide);
• Use of any other experimental drug or therapy within 28 days of baseline;
• Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs;
• Any prior use of lenalidomide;
• Concurrent use of other anti-cancer agents or treatments;
• Uncontrolled hyperthyroidism or hypothyroidism;
• Patients with history of idiopathic deep venous thrombus and/or pulmonary embolism within last three years;
• Neuropathy ≥ grade 2;
• 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)
• Current inclusion in other clinical trials;
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals