A Multicenter, Phase 1B, Open-Label Study to Determine the Safety and Activity of CC-292 in Combination With Lenalidomide in Subjects With Relapsed and /or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
- Male and female subjects 18 years of age and older at the time of signing the
informed consent document (ICD).
- Body weight at least 50 kg.
- Must have a documented diagnosis of CLL/SLL (International Workshop on Chronic
Lymphocytic Leukemia IWCLL Guidelines - Hallek 2008) by investigator assessment.
- Have failed at least 1 previous treatments for CLL/SLL, and have relapsed and/or
refractory disease following last prior treatment defined as CLL/SLL that does not
achieve at least a partial response (PR) to therapy or that progresses within 6
months of treatment.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or less.
- Life expectancy of at least 3 months from time of signing ICD.
- Females of childbearing potential (FCBP) must have a negative medically supervised
pregnancy test prior to starting study therapy and agree to ongoing pregnancy testing
during and after end of study therapy; commit to continued abstinence from
heterosexual intercourse or agree to use, comply with two effective methods of
contraception without interruption, 28 days prior to starting study drug, during
study therapy, and for 28 days after discontinuation of study therapy.
- Male subjects must agree to use a latex condom during sexual contact with a FCBP even
if they have had a vasectomy, throughout study drug therapy and dose interruption,
and for 28 days after end of study therapy; agree to not donate semen or sperm during
study drug therapy and for 28 days after end of study drug therapy.
- All subjects must understand that lenalidomide could have a potential teratogenic
risk, agree to abstain from donating blood with taking lenalidomide therapy and
following discontinuation of study drug therapy; have an echocardiogram (ECG) or
multigated acquisition (MUGA) scan of the heart demonstrating left ventricular
ejection fraction (LVEF) at least 50% or the institution's lower limit of normal;
have recovered from adverse, toxic effects of prior therapies to equal to or less
than 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse
Events [CTCAE] version 4.03 except for alopecia and peripheral neuropathy.
- Any significant medical condition, laboratory abnormality, or psychiatric illness
that would prevent the subject from participating in the study.
- Autologous stem cell transplant within 3 months prior to the time of signature on the
ICD Informed Consent Document.
- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection requiring parenteral antibiotics; uncontrolled diabetes mellitus; chronic
symptomatic congestive heart failure; unstable angina pectoris, angioplasty,
stenting, or myocardial infarctions within 6 months prior to the time of signature on
the ICD; clinically significant cardiac arrhythmia that is symptomatic or requires
treatment, or asymptomatic sustained ventricular tachycardia. Subjects with
controlled atrial fibrillation that is asymptomatic are eligible.
- Pregnant or lactating females.
- Prior history of malignancies, unless the subject has been free of the disease for 3
or more years prior to the time of signature on the ICD. Exceptions to the 3 or more
year time limit include history of basal cell carcinoma of the skin; squamous cell
carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the
breast; carcinoma in situ of the bladder; incidental histologic finding of prostate
cancer (Tumor/Nodes/Metastasis [TNM] stage pf T1a pr T1b
- Known seropositivity for or history of active viral infection with human
immunodeficiency virus (HIV).
- Known seropositivity for hepatitis C virus (HCV); hepatitis B virus (HBV).
- Subjects who are at a high risk for a thromboembolic event and are not willing/able
to take venous thromboembolic event (VTE) prophylaxis.
- Any of the following laboratory abnormalities:
1. Absolute Neutrophil Count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L)
2. Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow
involvement by lymphoma as demonstrated by recent bone marrow aspiration and
bone marrow biopsy
3. Serum Aspartate Transaminase/Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT)
or Alanine Transaminase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) >3.0 x
upper limit of normal (ULN) or > 5.0 x ULN in cases of documented liver
4. Serum bilirubin > 1.5 x ULN or > 3.0 x ULN in cases of Gilbert's Syndrome and
documented liver involvement by lymphoma;
5. Calculated creatinine clearance using the Cockcroft-Gault formula(Cockcroft,
6. Corrected QT interval (QTc) prolongation (defined as a QTc > 450 msec for males
and > 470 msec for females [Fredericia's correction] taken as average of 3
sequential ECGs taken 2 minutes apart) or other clinically significant ECG
abnormalities as assessed by the investigator.
- Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery
within 28 days of Day 1 dosing.
- Use of systemic corticosteroids in doses greater than prednisone equivalent to 20
mg/day within 3 weeks prior to study drug dosing.
- Concomitant use of medicines known to cause QT prolongation or torsades de pointes.
- Chronic use of H2 antagonists or proton pump inhibitors or their use within 7 days of
- Gastrointestinal abnormalities including the inability to take oral medication,
requiring intravenous alimentation, or prior surgical procedure affecting absorption.
- Prior treatment with Btk (Bruton's tyrosine kinase) inhibitors.
- Any live vaccinations within 3 weeks from first dose.
- History of hypersensitivity to immunomodulatory drugs (IMiDs) (eg, lenalidomide,
- Disease transformation (ie, Richter's Syndrome [lymphomas] or prolymphocytic
- Patients with uncontrolled hyper or hypothyroidism.