Antibiotic Therapy for early stage chronic lymphocytic leukaemia
- Conditions
- Chronic Lymphocytic LeukaemiaMedDRA version: 14.1Level: PTClassification code 10008958Term: Chronic lymphocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-022260-12-GB
- Lead Sponsor
- King's College Hospital NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
Group 1 Good risk stage A CLL
· Age = 18
· ECOG performance status of 2 or less.
· CLL with a typical immunophenotype
Clinical stage A disease. All of:
o B lymphocyte count >5x1000000000 /l
o Haemoglobin >10g/dl
o Platelets >100x1000000000/l
o Lymphadenopathy = 2 or fewer sites
· No disease progression over a minimum of 1 month prior to
commencement of therapy. All of:
o lymphocyte doubling time > 12 months
o stable blood counts: <1g/dl fall in haemoglobin, <50x1000000000/l fall in
platelets
o lymph nodes liver and spleen, <50% increase in size
· Less than 2 adverse prognostic factors from:
o CD38 expression >7%
o Unmutated Vh genes (>98% homology with germline)
· Absence of adverse cytogenetics
o Deletion of chromosome 11q22 (>20% by FISH)
o Deletion of chromosome 17p13 (>20% by FISH)
· Expected survival > 6 months
· Able to give informed consent
· No clinical evidence of active infection at the time of study entry
· No known allergy to any of the study medications
· Estimated GFR >60ml/min
· Liver function tests <1.5 x upper limit of normal
Group 2. Monoclonal B-lymphocytosis (MBL)
· Age = 18
· ECOG performance status of 2 or less.
· Clinical stage MBL. All of:
· B lymphocyte count >1.5x1000000000/l but <5x1000000000/l
. Haemoglobin >10g/dl
· Platelets >100x1000000000/l
· No lymphadenopathy
· MBL with a typical CLL immunophenotype
· No disease progression over a minimum of 1 month prior to commencement of therapy. All of:
· lymphocyte doubling time > 12 months
· stable blood counts: <1g/dl fall in haemoglobin, <50x1000000000/l fall in platelets
· Expected survival > 6 months
· Able to give informed consent
· No clinical evidence of active infection at the time
of study entry
· No known allergy to any of the study medications
· Estimated GFR >60ml/min
· Liver function tests <1.5 x upper limit of normal
Group 3: Adverse risk stage A CLL
· Age = 18
· ECOG performance status of 2 or less.
· CLL with a typical immunophenotype
· Diagnosis made within 6 months of date of screening.
· Clinical stage A disease. All of:
· B lymphocyte count >5x1000000000/l
· Haemoglobin >10g/dl
· Platelets >100x1000000000/l
· Lymphadenopathy = 2 or fewer sites
· No disease progression over a minimum of 1 month prior to commencement of therapy. All of:
· lymphocyte doubling time > 12 months
. stable blood counts: <1g/dl fall in haemoglobin, <50x1000000000/l fall in
platelets
. lymph nodes liver and spleen, <50% increase in size
· 2 poor prognostic factors and/or adverse cytogenetics
o CD38 expression =/>7%
o Unmutated Vh genes (>98% homology with germline)
AND/OR
o Adverse cytogenetics: either or both of:
§ Deletion of chromosome 11q22 (>20% by FISH)
§ Deletion of chromosome 17p13 (>20% by FISH)
· Expected survival > 6 months
· Able to give informed consent
· No clinical evidence of active infection at the time of study entry
· No known allergy to any of the study medications
· Estimated GFR >60ml/min
· Liver function tests <1.5 x upper limit of normal.
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 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180
· Disease progression during screening period
· Known positivity for HIV types 1 or 2
· Active infection at the time of screening
· Pregnancy or lactation
· Females of childbearing potential* and males not willing to practice an effective method of contraception whilst receiving the antibiotic regimen and for 4 weeks after the last dose
· Concomitant medication likely to produce serious interaction with study drugs including, but not limited to, warfarin type oral anticoagulants and anti-epileptics (For procedure to identify and classify adverse events
see appendix D)
* A woman of child-bearing potential is a sexually mature woman who has not undergone a hysterectomy or bilateral oopherectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate whether patients with previously untreated, early stage chronic lymphocytic leukaemia (CLL) respond to empirical broad spectrum antibiotics and therefore test the hypothesis that occult bacterial infection is responsible for the induction and maintenance of CLL.;Secondary Objective: To assess immune and inflammatory markers and microbial serology. To be performed if responses to antibiotic therapy are observed.;Primary end point(s): Overall response rate (Complete Remission (CR) + Partial Remission (PR)) at 6 months.;Timepoint(s) of evaluation of this end point: 6 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): i) Incidence of CTCAE grade 2 or above treatment related toxicity from day 1 to 6 weeks.<br><br>ii) Bone marrow minimal Residual Disease (MRD) status in patients who achieve CR at 6 months.<br><br>iii) Overall response rate (Complete Remission (CR) + Partial Remission (PR)) at 12 months based on clinical and peripheral blood measurements.<br>Please enter information in English and add any other language that is applicable;Timepoint(s) of evaluation of this end point: i) 6 weeks<br>ii) 6 months<br>iii) 12 months