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A Pilot Study to Establish the Safety & Efficacy of a Combination of Dexamethasone & Lenalidomide in Patients With Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL)

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia

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Trial Information

A Pilot Study to Establish the Safety & Efficacy of a Combination of Dexamethasone & Lenalidomide in Patients With Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL)

In this study we plan to assess the safety and tolerability of the combination of
dexamethasone, and lenalidomide (D+L) in patients with relapsed or refractory CLL, a
subgroup with limited treatment options. Lenalidomide offers an alternative way of treating
CLL. In a Phase 1 safety and pharmacokinetics study (study 1398/180) in healthy male
volunteers, it was demonstrated that lenalidomide administered at a dose of 100 mg twice a
day for 6 days had an acceptable safety profile with grade 1-2 rash and pruritus being the
primary adverse events associated with the administration of the compound. In myeloma and
MDS, lenalidomide has been studied mostly at two doses: 25 mg/day and 10 mg/day. In CLL
significant toxicity was observed with these two dose levels, including tumour lysis
syndrome and tumour flare.47,48 We therefore plan to start therapy with lenalidomide at a
relatively low dose of 5mg/day, days 1-28, with cycle 1 and escalate to the maximum dose of
10mg/day with cycles 2-12. We have elected to administer lenalidomide continuously as
opposed to pulsing over 14-21 days of each cycle to reduce the risk of tumour flare reaction
(TFR), when this agent is reintroduced with each cycle. Finally, lenalidomide will be
administered in combination with Dexamethasone, at a dose of 20mg/day for 4 days in each 28
day cycle as this allows convenient oral administration. We and others have demonstrated
that Dexamethasone level is effective in CLL patients who are refractory or have relapsed
following primary Fludarabine therapy. The combination of D+L will likely reduce toxicity,
especially TFR, whilst improving overall efficacy without promoting the emergence of
chemoresistant clones in which tumour suppressor genes have been inactivated.

Inclusion Criteria:

- Diagnosis of relapsed or refractory CLL as defined by the NCIWG criteria, requiring

- 1-3 lines of prior therapy

- Fludarabine- or Alemtuzumab-based therapy inappropriate

- WHO Performance status ≤2

- Age ≥ 18 years

- Life expectancy > 6 months

- Male and female subjects must meet the inclusion criteria for the Lenalidomide
Pregnancy Prevention Risk Management Plan.

- Male and female subjects must agree to follow the Lenalidomide Pregnancy Prevention
Risk Management Plan (including contraception 4 weeks before, during and 4 weeks
after treatment for females of child-bearing potential).

- Signed informed consent

Exclusion Criteria:

- Previously untreated CLL

- Fit patients for whom alemtuzumab or fludarabine- based therapy would be

- Creatinine clearance < 30ml/min calculated by Cockcroft-Gault

- Bilirubin > 1.5 x upper limit of normal

- Patients with marrow suppression resulting in significant cytopenia (Neutrophils <0.5
x 109/l, Platelets <30 x 109/l).

- Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy or other
investigational therapy within 4 weeks prior to study Day 1.

- Known infection with HIV, hepatitis B or hepatitis C.

- Uncontrolled glaucoma, diabetes mellitus, hypertension or symptomatic peptic ulcer

- Peripheral neuropathy > grade 1

- Proven or suspected transformation to aggressive B-cell malignancy (e.g. large
-B-cell lymphoma, Richter's syndrome, or PLL).

- Second malignancy requiring treatment other than non metastatic skin or prostate

- Any medical condition that would require long-term use (>1 month) of systemic
corticosteroids at a dose greater than 5mg/day of prednisolone during study

- Active uncontrolled bacterial, viral or fungal infections Cardiac failure, myocardial
infarction within 6 months prior to study day 1, or evidence of ischaemia on ECG
within 30 days prior to study day 1.

- Epileptic disorders requiring anticonvulsant therapy

- Major surgery, other than diagnostic surgery within 4 weeks prior to Study Day 1.

- Pregnant or currently breastfeeding.

- Patients who for other reasons are not expected to complete the study

- Subjects with a known allergy to allopurinol

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients who achieve objective response (CR + PR) according to the updated 1996 NCIWG criteria measured at 4 weeks after the completion of chemotherapy

Outcome Time Frame:

4 weeks after the completion of chemotherapy

Safety Issue:


Principal Investigator

Amit Nathwani

Investigator Role:

Principal Investigator

Investigator Affiliation:

University College, London


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

May 2012

Completion Date:

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • CLL
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid