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Pilot Study to Establish Safety & Efficacy of a Combination of Dexamethasone and Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukaemia (CLL) (LenD)

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Lenalidomide & Dexamethasone
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of relapsed or refractory CLL as defined by the NCIWG criteria, requiring treatment
  • 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 appropriate
  • 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 disease
  • 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 tumours
  • 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 treatment.
  • 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

Sites / Locations

  • Royal Liverpool University Hospital
  • University College London

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Lenalidomide & Dexamethasone

Arm Description

Lenalidomide, 5mg daily, increased to 10mg after 1st cycle. Dexamethasone, 20mg days 1-4 each cycle

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of response
Response will be assessed 4 weeks after completion or discontinuation of treatment. Response and disease status will be assessed at monthly follow up visits until 6 months post completion or discontinuation of treatment. After this patients will be assessed annually until death and the date of first relapse or progression will be recorded for every patient, therefore giving a duration of response in months.
Time to next treatment
Patients will be assessed after completion or discontinuation of treatment monthly until 6 months, and then assessed annually. At these assessments the patients status will be assessed and any further treatment for the disease will be recorded and the date of this treatment. Therefore the time from end of chemotherapy to next treatment will be recorded for each patient, in months.

Full Information

First Posted
October 18, 2011
Last Updated
November 7, 2016
Sponsor
University College, London
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1. Study Identification

Unique Protocol Identification Number
NCT01459211
Brief Title
Pilot Study to Establish Safety & Efficacy of a Combination of Dexamethasone and Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukaemia (CLL)
Acronym
LenD
Official Title
A Pilot Study to Establish the Safety & Efficacy of a Combination of Dexamethasone & Lenalidomide in Patients With Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to establish the safety and efficacy of a combination of dexamethasone and lenalidomide (Revlimid®) (D+L) in subjects with relapsed or refractory CLL who have failed or are unable to tolerate standard up-front therapy with regimens containing Fludarabine or in those with mutations in the p53 gene, CAMPATH-1H.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
CLL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide & Dexamethasone
Arm Type
Other
Arm Description
Lenalidomide, 5mg daily, increased to 10mg after 1st cycle. Dexamethasone, 20mg days 1-4 each cycle
Intervention Type
Drug
Intervention Name(s)
Lenalidomide & Dexamethasone
Other Intervention Name(s)
Revlimid
Intervention Description
Subjects with relapsed or refractory CLL will receive twelve 28-day cycles of treatment. Each cycle will consist of: Oral Dexamethasone (20mg daily, days 1-4), Oral Lenalidomide on days 1-28 of each cycle, starting at 5mg per day in cycle 1 in patients with creatinine clearance ≥ 60ml/min calculated by Cockcroft-Gault. The dose will be increased to 10mg per day with cycles 2-12 unless there is evidence of disease progression or unacceptable drug toxicity
Primary Outcome Measure Information:
Title
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
Time Frame
4 weeks after the completion of chemotherapy
Secondary Outcome Measure Information:
Title
Duration of response
Description
Response will be assessed 4 weeks after completion or discontinuation of treatment. Response and disease status will be assessed at monthly follow up visits until 6 months post completion or discontinuation of treatment. After this patients will be assessed annually until death and the date of first relapse or progression will be recorded for every patient, therefore giving a duration of response in months.
Time Frame
Time from initial response to first relapse/progression or death
Title
Time to next treatment
Description
Patients will be assessed after completion or discontinuation of treatment monthly until 6 months, and then assessed annually. At these assessments the patients status will be assessed and any further treatment for the disease will be recorded and the date of this treatment. Therefore the time from end of chemotherapy to next treatment will be recorded for each patient, in months.
Time Frame
Time from end of chemotherapy to next treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of relapsed or refractory CLL as defined by the NCIWG criteria, requiring treatment 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 appropriate 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 disease 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 tumours 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 treatment. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Nathwani
Organizational Affiliation
University College, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Liverpool University Hospital
City
Liverpool
Country
United Kingdom
Facility Name
University College London
City
London
ZIP/Postal Code
W1T 4TJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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