Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) MedDRA version: 20.0 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10008978 Term: Chronic lymphocytic leukemia refractory System Organ Class: 100000012991 MedDRA v
Conditions
Interventions
Product Name: CC-122
Product Code: CC-122
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-122
Current Sponsor code: CC-122
Other descriptive name: CC-122 active ingredient in capsule (AIC)
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subjects = 18 years age and = 80 years of age at the time of signing the informed consent form - Must have a documented diagnosis of CLL/SLL requiring treatment (IWCLL Guidelines for the Diagnosis and Treatment of CLL [Hallek, 2008]). In addition: a. Presence of at least one clinically measurable lesion: i. nodal lesion that measures = 1.5 cm in longest dimension (LD) and = 1.0 cm in longest perpendicular dimension (LPD) or ii. spleen that measures = 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement or iii. liver that measures = 20 cm in LVD with a minimum of 2 cm enlargement or iv. peripheral blood B lymphocyte count > 5000/uL - Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to = 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows: a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions: i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria 1. CIRS = 6 2. Creatinine Clearance 5.0 cm in diameter) are considered at higher risk for developing TFR and may only be enrolled upon discussion with the sponsor’s medical monitor and agreement to close medical management - Pregnancy Prevention Risk Management Plan: a. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in the PPRMP and pregnancy results must be negative b. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods o For Arm C, subjects must agree to use adequate contraceptive methods for 18 months c. Males (including those who have had a vasectomy) must practice complete abstinence or use barrier contraception (condoms) when
Exclusion criteria
Exclusion criteria: - Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study - Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study - Any condition that confounds the ability to interpret data from the study - Prior autologous or allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of signing the ICD. Subjects who received allogeneic SCT = 12 months before signing the ICD may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy -Uncontrolled intercurrent illness including, but not limited to: a. Ongoing or active infection requiring parenteral antibiotics. b. Uncontrolled diabetes mellitus. c. Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease). d. Active central nervous system involvement as documented by spinal fluid cytology or imaging. e. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia. f. Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with protocol. -History of second malignancies with life expectancy of 2 years from signing the ICD are eligible. -Known acute or chronic pancreatitis -Pregnant or lactating females Arm B only (CC-122 in combination with ibrutinib): - Prior treatment with a BTK inhibitor - Presence of transfusion-dependent thrombocytopenia or a h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Determine the safety of single agent CC-122 in subjects with relapsed/refractory CLL/SLL - Determine the safety and tolerability of the combination of CC-122 and ibrutinib and determine the RP2D of the combination in ibrutinib-naive CLL/SLL subjects - Determine the safety and tolerability of the combination of CC-122 and obinutuzumab and determine the RP2D of the combination in subjects with relapsed/refractory CLL/SLL;Secondary Objective: - Characterize CC-122 pharmacokinetics (PK) in subjects with CLL and assess potential drug-drug interactions when CC-122 is given in combination with ibrutinib, rituximab, or obinutuzumab - Determine ibrutinib concentrations when given alone or in combination with CC-122 - Determine the preliminary efficacy of single agent CC-122, the combination of CC-122 and ibrutinib, and the combination of CC-122 and obinutuzumab;Primary end point(s): 1)Incidence and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs 2)Determination of the NTD for CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab 3)Determination of the MTD for CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab;Timepoint(s) of evaluation of this end point: 1)adverse events, including DLT: will be monitored from the time of signing ICF through 28 days post IP discontinuation 2)Determination of the NTD : when = 2 out of 6 DLT evaluable subjects in a fixed-dose cohort experience an IP-related DLT 3)Determination of the MTD: when at least 6 subjects have been enrolled and = 1 subjects have experienced a DLT during the DLT evaluation period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1)CC-122 plasma concentrations when administered alone or in combination with ibrutinib or obinutuzumab 2)CC-122 pharmacokinetic parameters when administered in combination with ibrutinib 3)Ibrutinib plasma concentrations and/or pharmacokinetic parameters when administered in combination with CC-122 4)Best overall response (BOR) [CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, partial response with lymphocytosis (PRL) (applicable to Arm B only)] 5)Minimal Residual Disease (MRD) negativity rate 6)Duration of response (DoR) 7)Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: 1) ArmA:C1,C2 D1/D15; C3&C5 D15 ArmB:C1D1;C2 D1/D15 ArmC:C1D9/D22 2)C1D1;C2D1/D15 Expansion Phase 3)C1D1;C2D1/D15 escalation phase; C1D1; C2D1/D15 Expansion Phase 4) End of cycle 6. Additional CT scan(s) is allowed if clinically indicated until documented PD or initiation of subsequent CLL therapy. 5)At time of CR/CRi confirmation visit at the time of PR (within 12wk after clinical and lab response criteria are met) and approx. every 6cycles thereafter if patient still MRD+ 6)End of cycle 6.Additional CT scan(s) is allowed if clinically indicated until documented PD or initiation of subsequent CLL therapy. 7)every cycle | — |
Countries
Austria, Germany, Italy, Spain, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed