This research study is for patients who have been newly diagnosed with diffuse large B-cell
lymphoma DLBCL and are receiving treatment for the first time.
This study will be conducted in two phases. Phase 1 will test the safety of increasing dose
levels of CC-122 when given in combination with R-CHOP-21 therapy to identify an appropriate
dose and schedule for further evaluation in Phase 2. Phase 2 will evaluate the rate of
complete response when adding CC-122 to the R-CHOP-21 regimen in first-line treatment of
patients with poor risk DLBCL.
This study is separated into three periods: the Screening period, the Treatment period and
the Follow-up period. Before the patient can receive the drug the doctor will perform test to
find out whether he/she can participate in the study. This is done during the Screening
period. If the patient and the treating physician determine that the patient is eligible to
participate in the study, the patient will be registered in the study and receive CC-122
combined with R-CHOP.
In the Treatment period the patient will receive treatment for up to 6 treatment cycles. Each
treatment cycle is 21 days long. The full length of the treatment period will be
approximately 4 months.
The follow-up period begins when the patient has completed treatment or is discontinued for
any reason. During the follow-up period the patient will have fewer exams, test and visits.
The first follow-up visit will be 28 days after treatment is completed or discontinued. After
that, the follow-up visits will be every 3 months during the first year, then every 6 months
until the study is closed.
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Subject has documented, histologically locally confirmed, previously untreated CD20+
DLBCL (NOS) per World Health Organization (WHO) classifications (Swerdlow, 2008).
3. Subject is considered an appropriate candidate (per Investigator assessment) for
induction therapy with 6 cycles of R-CHOP-21 immunochemotherapy.
4. Subject has a performance status (PS) of 0-2 according to the Eastern Cooperative
Oncology Group (ECOG) scale. Subjects with ECOG PS of 3 may be included if decreased
PS is secondary to DLBCL only, and not to comorbidities.
5. Subject has poor-risk disease defined as International Prognostic Index (IPI) score ≥
3 (high-intermediate or high-risk classification).
6. Subject has measurable disease on cross-sectional imaging by computed tomography (CT)
with at least one (post-biopsy) measurable lesion ≥ 2.0 cm in its longest dimension.
7. Subject must appropriately be able to complete Screening assessments before beginning
treatment for DLBCL, in the judgement of the Investigator.
For subjects with bulky disease, B-symptoms, compressive disease, elevated bilirubin due to
lymphoma, rapidly progressing adenopathies, or worsening performance status, pre-phase
treatment with up to 100 mg/day prednisone, or equivalent, for a maximum of 10 days is
permitted prior to beginning the treatment period, at the discretion of the Investigator. A
washout period is not required, however, the Screening positron emission tomography (PET),
CT, tumor biopsy (if needed), and bone marrow biopsy (if needed) should be completed before
8. Subject's central laboratory values must fulfill the following requirements during
Screening: Blood product transfusions and hematopoietic growth factors may not be used to
meet eligibility criteria. Screening samples should not be collected within 14 days after
subject receives a blood product transfusion or growth factors.
1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) unless secondary to
extensive bone marrow involvement by lymphoma (ie, ≥ 50%) as demonstrated by
unilateral bone marrow core biopsy performed during Screening or within 3 months prior
to signing the ICF. In the case of documented extensive bone marrow involvement an ANC
≥ 1,000 cells/mm3 (1.0 x 109/L) is required.
2. Platelet count ≥ 100,000/mm3 (100 x 109/L) unless secondary to extensive bone marrow
involvement by lymphoma (ie, ≥ 50%) as demonstrated by unilateral bone marrow core
biopsy performed during Screening or within 3 months prior to signing the ICF. In the
case of documented extensive bone marrow involvement, a platelet count of ≥ 75,000/
mm3 (75 x 109/L) is required.
3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3.0 x
upper limit of normal (ULN). In the case of documented liver involvement by lymphoma,
ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
4. Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L). In the case of Gilbert's syndrome, or
documented liver or pancreatic involvement by lymphoma, serum total bilirubin must be
≤ 5.0 mg/dL (86 μmol/L).
5. Calculated creatinine clearance (CrCl) of ≥ 50 mL/min by the Cockcroft-Gault formula.
9. Subject must understand and voluntarily sign an Informed Consent Form (ICF) prior to any
study-specific assessments/procedures being conducted.
10. Subject is willing and able to adhere to the study visit schedule and other protocol
11. Sufficient tissue from diagnostic tumor/ lymph node biopsy (from within 2 months prior
to ICF signature) must be available for translational research purposes or subject is
willing to undergo core needle or incisional/ excisional biopsy during Screening.
12. Females of childbearing potential (FCBP)1 must:
1. Agree to use two reliable forms of contraception simultaneously or to practice
complete abstinence (True abstinence is acceptable when this is in line with the
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar,
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable
methods of contraception.) from heterosexual contact during the following time periods
related to this study: 1) for at least 28 days before starting CC-122; 2) while taking
CC-122; 3) during dose interruptions; and 4) for at least 28 days after the last dose
of CC-122 as specified in the Pregnancy Prevention and Risk Management Plan (PPRMP)
2. Have a negative result confirmed for a medically supervised urine (or serum) pregnancy
test (with a sensitivity of at least 25 mIU/mL) 10-14 days prior to the first dose of
IP. A second pregnancy test performed within 24 hours prior to the first dose of IP
must also be confirmed to be negative prior to IP administration.
13. Avoid conceiving for at least 12 months after the last dose of rituximab, or according
to the local rituximab Prescribing Information or Summary of Product characteristics
(SmPC); at least 28 days after the last dose of any other study drug.
1. Agree to ongoing pregnancy testing during the course of the study as outlined in the
14. Male subjects must:
1. Practice complete abstinence (True abstinence is acceptable when this is in line with
the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar,
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable
methods of contraception.) or agree to use a condom during sexual contact with a
pregnant female or a FCBP for at least 12 months after the last dose of rituximab.
2. Agree to not donate semen or sperm for at least 12 months following the last dose of
15. All subjects must:
1. Understand that CC-122 could have a potential teratogenic risk.
2. Agree to abstain from donating blood while taking IP and for at least 28 days
following discontinuation of IP.
3. Agree not to share IP with another person
4. Be counseled about pregnancy precautions and risks of fetal exposure and agree to
requirements of the Pregnancy Prevention and Risk Management Plan (PPRMP)
16. Subject is able to swallow pills.
1. Subject is seropositive for or has active viral infection with hepatitis B virus (HBV):
1. HBV surface antigen (HBsAg) positive
2. HBV surface antigen (HBsAg) negative, HBV surface ant ibody (ant i-HBs) posit ive
and/or HBV core antibody (ant i-HBc) positive, and detectable viral DNA Subjects who
are seropositive because of prior HBV vaccination are eligible (anti- HBs positive,
anti-HBc negative, and HBsAg negative).
2. Subject is known to be seropositive for, or have an active infection with, hepatitis C
3. Subject is known to be seropositive for, or have an active infection with, human
immunodeficiency virus (HIV).
4. Subject has any neuropathy > Grade 1. 5. Subject has impaired cardiac function or
clinically significant cardiac diseases, including any of the following:
1. Left ventricular ejection fraction (LVEF) < 45% as determined by multi-gated
acquisition scan (MUGA) or echocardiogram (ECHO).
2. Complete left bundle branch or bifascicular block.
3. Congenital long QT syndrome
4. Persistent or clinically meaningful ventricular arrhythmias.
5. QTcF > 460 msec on Screening electrocardiogram (ECG)
6. Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting
treatment in the study.
7. Troponin-T value > 0.4 ng/mL or B-type natriuretic protein (BNP) > 300 pg/mL by
central laboratory assessment Subjects with baseline troponin-T > ULN or BNP > 100
pg/mL are eligible but must have a cardiologist evaluation prior to enrollment in the
trial for baseline assessment and optimization of cardioprotective therapy.
6. Subject has confirmed central nervous system (CNS) involvement by DLBCL. Subjects at
risk for CNS involvement per Investigator assessment must receive prophylaxis. For subjects
at risk, or with any neurological symptoms, testing for CNS involvement is required at
7. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.
8. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.
9. Subject has any condition that confounds the ability to interpret data from the study.