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

November 7, 2016 updated by: University College, London

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Liverpool, United Kingdom
        • Royal Liverpool University Hospital
      • London, United Kingdom, W1T 4TJ
        • University College London

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Lenalidomide & Dexamethasone
Lenalidomide, 5mg daily, increased to 10mg after 1st cycle. Dexamethasone, 20mg days 1-4 each cycle
Drug: Lenalidomide & Dexamethasone

Subjects with relapsed or refractory CLL will receive twelve 28-day cycles of treatment. Each cycle will consist of:

  1. Oral Dexamethasone (20mg daily, days 1-4),
  2. 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
Other Names:
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
4 weeks after the completion of chemotherapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of response
Time Frame: Time from initial response to first relapse/progression or death
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 from initial response to first relapse/progression or death
Time to next treatment
Time Frame: Time from end of chemotherapy 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.
Time from end of chemotherapy to next treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University College, London

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Amit Nathwani, University College, London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 18, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UCL/09/387

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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