A phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of lenalidomide (Revlimid®) as maintenance therapy for patients with B-cell chronic lymphocytic leukemia following second-line therapy

Summary

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will compare the efficacy and safety of oral lenalidomide maintenance therapy to that of placebo maintenance therapy in patients with B-cell CLL who achieved at least partial response (PR) with second line therapy.

There will be 400 patients enrolled and randomized (1:1) into two study arms: placebo daily or lenalidomide 2.5 mg daily on days 1-28 of the first 28 day cycle. If the 2.5 mg dose level is well tolerated, escalation to 5 mg daily on days 1-28 of each 28-day cycle is permitted starting with the second cycle; for those patients who tolerate well the 5 mg dose and may improve further their response, escalation to 10 mg daily on days 1-28 for each 28-day cycle after 5 continuous cycles at 5 mg will be permitted.

The endpoint of the study are:

* Primary endpoints
o Overall Survival
o Progression- Free Survival

* Secondary endpoint
o Safety
o Tumor response, including evaluation of minimal residual disease by flow cytometry
o Duration of response
o Health-related quality of life by functional assessment of cancer therapy-leukemia and EQ-5D

* Exploratory endpoint
o Cytogenetic fluorescence in situ hybridization (FISH), biomarker analyses, and flow cytometry
o Beta-2 Microglobulin
o Pharmacoeconomic/clinical benefit

We plan to enroll about 5 subjects at our site and the protocol target enrollment is 400 subjects. This study will be open for 20 months of enrollment. All patients who tolerate lenalidomide may continue receiving the drug until disease progression, intolerable toxicity occurs, withdrawal of consent and/or the investigator determines that further therapy is not in the patient[Right Quote]s best interest.
Screening Procedures
Subjects may have to fill out certain forms or have the following exams, tests or procedures:

* Collection of information about medical history, including cancer history and treatment history for B-cell CLL.

* A review of any medications the subject has used in the 28 days (4 weeks) prior to starting study medication and review of contraception methods that will be utilized while participating in this study.

* A complete physical exam including measurement of vital signs (including weight and height), performance status will be assessed, and a 12-lead EKG. The physical exam will include assessment of liver, spleen, and lymph nodes.

* A bone marrow aspiration and a biopsy to confirm disease status.

* Blood samples for blood counts, blood chemistry test, thyroid test, immunoglobulins, , immune cells tests and a direct antiglobulin test (approximately 3 tablespoons).

* For females who are able to become pregnant, a urine pregnancy test will be performed.

* If subject is a man and has a partner who is able to have children, they must agree to use a condom from the start of study drug to 28 days (4 weeks) after the treatment discontinuation visit

* CT (computerized tomography) scans of the chest, abdomen, and pelvis will be performed to confirm disease status.

* This visit will last approximately 4-5 hours.

Participant Eligibility

1. Must understand and voluntarily sign an informed consent form.
2. Age ≥ 18 years at the time of signing the informed consent form.
3. Must be able to adhere to the study visit schedule and other protocol
requirements.
4. Must have a documented diagnosis of B-cell CLL (IWCLL guidelines for the
diagnosis and treatment of chronic lymphocytic leukemia, [Hallek, 2008]).
5. Must have been treated with a purine analog- or bendamustine- containing
regimen in the first and/or second line induction therapy. Alemtuzumabcontaining
regimens in place of purine analog- or bendamustine- containing
regimens will also be allowed for those patients with 17p deletion.
6. Must have achieved a minimum response of partial response (PR, nPR, CRi,
CR and MRD-negative CR) (IWCLL guidelines for the diagnosis and treatment
of chronic lymphocytic leukemia, [Hallek, 2008] Appendix 22.4) following
completion of second-line induction therapy prior to randomization
(documentation of response status must be available). Second-line induction
therapy must be documented to have been of sufficient duration.
7. Must have completed last cycle of second-line induction no less than 8 weeks
(56 days) and no greater than 20 weeks (140 days) prior to randomization.
8. Must have an Eastern Cooperative Oncology Group (ECOG) performance
status score of ≤2.
9. Females of childbearing potential (FCBP)† must:
 Have two negative medically supervised pregnancy tests prior to starting of
† Definitionstudy therapy. She must agree to ongoing pregnancy testing during the
course of the study, and after end of study therapy. (see specifics in
Appendix 22.10). This applies even if the subject practices complete and
continued sexual abstinence.
 Either commit to continued abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to
comply with, effective contraception without interruption, 28 days prior to
starting study drug, during the study therapy (including dose interruptions),
and for 28 days after discontinuation of study therapy, (see specifics in
Appendix 22.10).
10. Male subjects must:
 Commit to continued abstinence from heterosexual contact or agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy. (See specifics in Appendix
22.10)
 Agree to not donate semen during study drug therapy and for a period after
end of study drug therapy (see specifics in Appendix 22.10).
11. All subjects must:
 Have an understanding that the study drug could have a potential
teratogenic risk.
 Agree to abstain from donating blood while taking study drug therapy and
following discontinuation of study drug therapy. (See specifics in Appendix
22.10)
 Agree not to share study medication with another person.
 All subjects must be counseled about pregnancy precautions and risks of
fetal exposure. See Appendix 22.10.