Celgene 009

 A Phase 2, Multi-Center, Randomized, Double-Blind, Parallel-Group Study Of The Safety And Efficacy Of Different Lenalidomide (Revlimid®) Dose Regimens In Subjects With Relapsed Or Refractory B-Cell Chronic Lymphocytic Leukemia.

Must understand and voluntarily sign an informed consent form.

Age ≥18 years at the time of signing the informed consent form.

Must be able to adhere to the study visit schedule and other protocol requirements.

Must have a documented diagnosis of B-cell CLL [iwCLL guidelines for diagnosis and treatment of CLL (Hallek, 2008)] meeting at least one of the following criteria:

• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia. 

• Massive (i.e.,>6cm below the left costal margin) or progressive or symptomatic splenomegaly.

• Massive nodes (i.e., >10cm in longest diameter) or progressive or symptomatic lymphadenopathy.

• Progressive lymphocytosis with an increase of >50% over a 2 month period, or lymphocyte doubling time (LDT) of less than 6 months.

• A minimum of any one of the following disease-related symptoms must be present:

• Unintentional weight loss ≥10% within the previous 6 months.

• Significant fatigue (i.e., ECOG PS 2; cannot work or unable to perform usual activities).

• Fevers of greater than 100.5° F or 38.0° C for 2 or more weeks without other evidence of infection.

• Night sweats for more than 1 month without evidence of infection.

Must be relapsed or refractory to at least 1 but no more than 4 prior regimen(s) for treatment of CLL [relapsed/refractory as defined per the iwCLL guidelines for diagnosis and treatment of CLL (Hallek, 2008)].  At least one of the prior treatment must have included a purine analog-based regimen. Relapsed is defined as a subject who has previously achieved the criteria of a complete remission (CR) or partial remission (PR), but after a period of ≥6 months, demonstrates evidence of disease progression. Refractory is defined as treatment failure [e.g. Stable Disease (SD), non response, or progressive disease] or disease progression within 6 months to the last antileukemic therapy.

Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≥2.

Females of childbearing potential (FCBP) must:

• Have a negative medically supervised pregnancy test prior to starting study drug.  She must agree to ongoing pregnancy testing during study therapy and after discontinuation of study drug. This applies even if the subject practices complete and continued sexual abstinence.

• Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, prior to starting study drug, during study drug therapy, and after discontinuation of study drug.

Male subjects must:

• Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, during study drug therapy and after discontinuation of study drug.

All subjects must:

• Have an understanding that the study drug could have a potential teratogenic risk.

• Agree to abstain from donating blood during study drug therapy and after discontinuation of study drug.

• Agree not to share study drug with another person.

• Be counselled about pregnancy precautions and risks of fetal exposure.

   

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

Active infections requiring systemic antibiotics.

Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide.

Alemtuzumab therapy within 120 days of initiating lenalidomide treatment.

More than 4 prior regimens for treatment of CLL.

Prior therapy with lenalidomide. 

History of grade 4 rash due to prior thalidomide treatment.

Planned autologous or allogeneic bone marrow transplantation.

Pregnant or lactating females.

Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to initiating study drug.

Prior history of malignancies, other than CLL, unless the subject has been free for ≥2 years. Exceptions include the following:

• Basal cell carcinoma of the skin. 

• Squamous cell carcinoma of the skin. 

• Carcinoma in situ of the cervix.

• Carcinoma in situ of the breast.

• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).

• History of renal failure requiring dialysis.

 Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.

Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).

Any of the following laboratory abnormalities:

• Calculated (method of Cockroft-Gault) creatinine clearance of <60 mL/min (creatinine clearance may also be obtained by the 24-hour collection method at the investigator’s discretion).

• Absolute neutrophil count (ANC) < 1,000/μL (1.0 X 10⁹/L).

• Platelet count < 50,000/μL (50 X 10⁹/L).

• Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN). 

• Serum total bilirubin > 1.5 x ULN.

Uncontrolled hyperthyroidism or hypothyroidism.

Venous thromboembolism within 12 months.

≥ Grade-2 neuropathy.

Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.

Disease transformation [i.e. Richter’s Syndrome (lymphomas) or prolymphocytic leukemia].

Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy.

Known presence of alcohol and/or drug abuse.

Research Nurse

Lindsay Taylor

Tel 0113 2067420

Email Lindsay.Taylor@leedsth.nhs.uk

Research Nurse

David Buchanan

Tel 0113 2067436

Email david.buchanan@leedth.nhs.uk

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