To investigate the feasibility and efficacy of a maximum of 6 cycles of Chlorambucil with Rituximab plus Lenalidomide at the RDL.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part I:
* Dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended
phase II dose (RDL) of Chlorambucil when combined with Rituximab and
Lenalidomide.
Part II:
* CR+PR rate
Secondary outcome
Part I
* Toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR)
and neutropenic sepsis
Part II
* Improvement of response due to lenalidomide
* Toxicity, especially tumor lysis syndrome (TLS), tumor flare reaction (TFR)
and neutropenic sepsis
* Progression free survival (PFS; i.e. time from registration to progression or
death from any cause, whichever comes first)
* Event-free survival (EFS; i.e. time from registration to induction failure,
progression or death from any cause, whichever comes first.
Background summary
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western
world mainly affecting the elderly. Although recently novel regimes containing
the chemotherapeutic agents fludarabine and cyclophosphamide in combination
with the monoclonal antibody rituximab (FCR) has shown improved progression
free and overall survival, this regimen is considered too toxic for elderly
patients. For the standard treatment of this patient group, chlorambucil,
response rates and duration are limited. A recent study showed that addition of
rituximab to chlorambucil improved the overall response rate but level of
responses remained poor. Lenalidomide, a novel immunomodulating agent is
thought to act by interaction in crosstalk between the microenvironment and
leukemic cells and has promising clinical activity in CLL. This study will test
the hypothesis that addition of lenalidomide to chlorambucil and rituximab will
result in improved response rates for elderly and young FCR unfit patients with
acceptable toxicity.
Study objective
To investigate the feasibility and efficacy of a maximum of 6 cycles of
Chlorambucil with Rituximab plus Lenalidomide at the RDL.
Study design
Phase II, prospective, multicenter
Intervention
Patients will be treated with 6 cycles of chlorambucil, rituximab, lenalidomide
followed by 6 cycles of lenalidomide
Study burden and risks
. Risks for the patient relate to drug specific side-effects, in particular
tumor flare reaction, tumor lysis and neutropenic sepsis.
Postbus 7057
1007 MB Amsterdam
NL
Postbus 7057
1007 MB Amsterdam
NL
Listed location countries
Age
Inclusion criteria
* Diagnosis of CLL without prior treatment;
* Patients with symptomatic stage A , according to IWCLL guidelines or stage B or stage C
* Age * 65 years at the time of signing the informed consent form, or age <65 years and CIRS * 7
* Able to adhere to the study visit schedule and other protocol requirements.
* WHO performance status of * 2;
* Laboratory test results within these ranges: ANC * 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;
* 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 pre-menopausal women). 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022294-34-NL |
| CCMO | NL35255.018.11 |