ENHANCE: A Phase 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT02406742
Collaborator
(none)
47
Enrollment
24
Locations
3
Arms
59.4
Actual Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Safety, pharmacokinetics, and preliminary efficacy of CC-122 alone and in combination with ibrutinib and obinuzutumab.

CC-122 has multiple activities, including immune modulation of several immune cell subsets and antiproliferative activity in CLL. CC-122 has also been shown to have a tolerable safety profile with some preliminary signs of efficacy with early human experience.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Detailed Description

The primary objectives of this Phase 1/2 Study are to determine the safety of single agent CC-122 and the safety, tolerability, and RP2D of CC-122 when administered in combination with ibrutinib and in combination with obinutuzumab to subjects with CLL/SLL. The secondary objectives are to evaluate the PK profiles of subjects administered CC-122 in combination with ibrutinib and in combination with obinutuzumab, to determine ibrutinib concentrations when given alone and in combination with CC-122 and to evaluate the preliminary efficacy of CC-122 at selected dose levels/regimens.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 Study to Determine the Safety, Pharmacokinetics, and Efficacy of Single Agent CC-122 and the Combinations CC-122 AND Ibrutinib and CC-122 and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Actual Study Start Date :
Jul 27, 2015
Actual Primary Completion Date :
Jul 7, 2020
Actual Study Completion Date :
Jul 7, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: CC-122 Single Agent

An intrasubject dose escalation design was selected to determine the safety of single agent CC-122 (Arm A) in order to reach an optimal, clinically active dose and to mitigate the risk of early tumor flare reactions, based on earlier experience with lenalidomide monotherapy in CLL.

Drug: CC-122
CC-122 will be administered daily starting at Cycle 1 Day 1 in 28-day cycles until disease progression, unacceptable toxicity, or discontinuation for any other reason.

Experimental: CC-122 in combination with ibrutinib

Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and ibrutinib to determine the NTD, MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee. The RP2D of the combination may be evaluated in ibrutinib-naïve and high-risk CLL patients in the dose expansion phase to continue to evalute safety and efficacy.

Drug: CC-122
CC-122 will be administered daily starting at Cycle 1 Day 1 in 28-day cycles until disease progression, unacceptable toxicity, or discontinuation for any other reason.

Drug: Ibrutinib

Experimental: CC-122 in combination with obinutuzumab

Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and obinutuzumab to determine the , MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee.. The RP2D of the combination may be evaluated in CLL patients who failed a B-cell receptor pathway inhibitor or venetoclax in the dose expansion phase to continue to evalute safety and efficacy.

Drug: CC-122
CC-122 will be administered daily starting at Cycle 1 Day 1 in 28-day cycles until disease progression, unacceptable toxicity, or discontinuation for any other reason.

Drug: Obinutuzumab
Obinutuzumab will be administered as an intravenous (IV) infusion at a dose of 100 mg on Cycle 1 Day 1 and 900 mg on Cycle 1 Day 2 and 1000 mg on Cycle 1 Days 8 and 15. The dose of obinutuzumab on Days 1 and 2 of Cycle 1 may be adjusted per institutional practice as long as the combined dose equals 1000 mg. Obinutuzumab will be administered at a dose of 1000 mg on Day 1 of Cycles 2 through 6.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants and Severity of AEs [Approximately 60 Months]

    Number and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs

  2. Determination of Non Tolerated Dose (NTD) and Maximum Tolerated Dose (MTD) [52 weeks]

    Determination of the NTD and MTD in CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab

Secondary Outcome Measures

  1. CC-122 Plasma Concentrations When Administered Alone or in Combination With Ibrutinib or Obinutuzumab [Approximately 60 Months]

    CC-122 plasma concentrations when administered alone or in combination with ibrutinib or obinutuzumab

  2. Ibrutinib Plasma Concentrations When Administered in Combination With CC-122 [Approximately 60 Months]

    Geometric mean concentration of Ibrutinib when administered alone or in combination with CC-122

  3. Best Overall Response (BOR) [Approximately 60 Months]

    Best overall response [CR, CRi, nPR, PR, PRL (applicable to Arm B only)] CR = Complete Response CRi = Complete response with incomplete marrow recovery nPR = nodular Partial Response PR = Partial response PRL= Partial response with lymphocytosis

  4. Minimal Residual Disease Response Rate [Approximately 60 Months]

    Minimal Residual Disease Response Rate in bone marrow and peripheral blood

  5. Duration of Response [Approximately 60 Months]

    measured from the time the response is first met until the first date that progressive disease or death is documented. Participants who neither progress nor die or who withdrew consent or are lost to follow-up prior to documentation of progression will be censored at the date of their last adequate response assessment.

  6. Progression Free Survival (PFS) [Approximately 60 Months]

    will be calculated as the time from irst IP (i.e. any study drug) dose date to the first documented progression or death due to any cause during or after the treatment period, whichever occurs first.

  7. Cmax When Administered Alone or in Combination With Ibrutinib [Approximately 60 Months]

    Peak (maximum) drug plasma concentration

  8. Tmax of CC-122 When Administered Alone or in Combination With Ibrutinib [Approximately 60 Months]

    Time to peak (maximum) drug concentration

  9. AUC of CC-122 When Administered Alone or in Combination With Ibrutinib [Approximately 60 Months]

    Area under the concentration -time curve calculated to the last observable concentration at time t

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed consent form.

  2. Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.

  3. Able to adhere to the study visit schedule and other protocol requirements.

  4. Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL guidelines). In addition:

  1. 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.
  1. 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:
  1. 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 < 70 mL/min; 3. Subject is not a candidate for a chemoimmunotherapy in the opinion of investigator. ii. Treatment with an approved BTK inhibitor is not required if subject has contraindications or is not a candidate for such a therapy in the opinion of the investigator. b. For Arm B, subjects with treatment-naïve or R/R CLL must meet the following criteria: i. Dose Escalation Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have either R/R CLL or treatment naïve (ie, first-line) CLL if the subject:

  2. has 17p- and/or TP53 mutation; or

  3. is unfit for standard chemoimmunotherapy meeting at least 1 of the following co-morbidity criteria: a. CIRS ≥ 6; b. Creatinine Clearance < 70 mL/min; c. Subject is not a candidate for a chemoimmunotherapy in the opinion of the investigator. The reason for not being a candidate must be documented in CRF. ii. Dose Expansion Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have high risk CLL. High risk is defined as: 1) 17p- and/or TP53 mutation positive in treatment naïve CLL; or 2) 17p- and/or TP53 mutation positive, and/or complex karyotype, and/or progression < 24 months after completion of 1st line chemoimmunotherapy in R/R CLL c. Subjects with R/R SLL or CLL with bulky disease (at least one lymph node measuring > 5.0 cm in diameter) are considered at higher risk for developing a TFR and may only be enrolled upon discussion with the sponsor's medical monitor and agreement to close medical management.

  4. Subjects must have the following lab values:

  5. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to bone marrow involvement by disease.

  6. Platelet count ≥ 100,000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x 109/L) if secondary to bone marrow involvement by disease.

  7. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x upper limit of normal (ULN) unless due to disease.

  8. Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.

o Serum bilirubin ≤ 1.0 x ULN unless due to Gilbert's syndrome, Treatment Arm B only (CC-122 in combination with ibrutinib)

  1. Calculated creatinine clearance of ≥ 60 ml/min.

  2. No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).

  3. ECOG PS (Eastern Cooperative Group Performance Status) of 0 or 1. 8. Ability to swallow oral capsules without difficulty. 9. Pregnancy Prevention Risk Management

Plan:
  1. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in the Pregnancy Prevention Risk Management Plan (PPRMP) and pregnancy results must be negative.

  2. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in the PPRMP.

*For Arm C, subjects must agree to use adequate contraceptive methods for 18 months (please refer to the obinutuzumab IB, PI, and SmPC).

  • Complete abstinence is only acceptable in cases where this is the preferred and usual lifestyle of the subject.

  • Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable.

  1. Males (including those who have had a vasectomy) must practice complete abstinence or use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in the PPRMP.

  2. Males must agree not to donate semen or sperm for the duration of the study and for 3 months after the last dose of CC-122.

  3. All subjects must:

  • Understand that the (investigational Product) IP could have a potential teratogenic risk.

  • Agree to abstain from donating blood while taking IP and following discontinuation of IP.

  • Agree not to share IP with another person.

  1. Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn.

  2. Be counseled about pregnancy precautions and risks of fetal exposure.

ARM B ONLY:
  1. Enrollment into Arm B will be permitted if ibrutinib is considered the standard of care in the clinical practice.
EXPANSION COHORT 2 OF ARM C:
  1. Subjects in Cohort 2 of Arm C must meet the following criteria:

  2. Subject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax;

  3. Subject must be either resistant to or intolerant of (ie., treatment failures) the last BCR PI and/or venetoclax. Resistant is defined as relapsed or refractory per

IWCLL2008:
  1. Relapse is defined as a patient who has previously achieved a CR or PR, but after a period of 6 or more months, demonstrates evidence of disease progression. ii. Refractory is defined as failing to achieve a CR or PR, or disease progression within 6 months after initiation of treatment with an approved BTK or PI3K inhibitor (eg, ibrutinib, idelalisib) or venetoclax. iii. Intolerance is defined as the inability to continue treatment with a BCR PI or venetoclax due to toxicities or due to development of a contraindication that makes the subject ineligible to receive further treatment with a BCR PI or venetoclax.
Exclusion Criteria:
  1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

  2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

  3. Any condition that confounds the ability to interpret data from the study.

  4. 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.

  5. Uncontrolled intercurrent illness including, but not limited to:

  6. Ongoing or active infection requiring parenteral antibiotics.

  7. Uncontrolled diabetes mellitus.

  1. The glycemic targets for subjects with diabetes should take into consideration age, comorbidities, life expectancy, and functional status of the subjects and follow established guidelines (eg, International Diabetes Federation, the European Diabetes Working Party guidelines, and the American Diabetes Association). For younger (< 70 years old) or subjects with life expectancy ≥ 10 years, the target glycosylated hemoglobin, type A1C (HbA1c) should be < 7.0%. The target HbA1c for older (≥ 70 years old) subjects or subjects with life expectancy < 10 years should be < 8.0%. Consultation with an endocrinologist is recommended when deciding if diabetes is optimally controlled.

  2. 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.

  1. History of second malignancies with life expectancy of < 2 years or requirement of therapy that would confound study results. This does not include the following:

  2. Basal cell carcinoma of the skin.

  3. Squamous cell carcinoma of the skin.

  4. Carcinoma in situ of the cervix.

  5. Carcinoma in situ of the breast.

  6. Carcinoma in situ of the bladder.

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

  8. Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV), or hepatitis B or C virus (HBV, HCV).

  1. Hepatitis B screening is mandatory for all patients (HBsAg and anti-HBc). Patients with active hepatitis B disease should not be treated with obinutuzumab. Patients should be referred to a specialist if they are carriers before treatment starts (see PI or SmPC). Subjects who are positive for anti-HBc and/or anti-HBs but negative for HBsAg and HBV DNA may be treated after consultation with a hepatologist.
  1. Any peripheral neuropathy ≥ NCI CTCAE Grade 2.

  2. Use of systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day.

  3. Medicines with high probability to cause QT prolongation or torsades de pointes. Subjects on chronic medications in this category may enroll after discussion with the medical monitor if changing these medications are not in the best medical interest of the patient.

  4. History of hypersensitivity to IMiDs® (lenalidomide, pomalidomide, thalidomide).

  5. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

  6. Left ventricular ejection fraction (LVEF) < 45% as determined by MUGA scan or echocardiogram (ECHO).

  7. Complete left bundle branch, or bifasicular, block.

  8. Congenital long QT syndrome.

  9. Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation.

  10. QTcF > 470 msec on Screening ECG (mean of triplicate recordings).

  11. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC

  12. Uncontrolled congestive heart failure or uncontrolled hypertension.

  13. Troponin-T value >0.4 ng/mL or BNP >300 pg/mL. Subjects with baseline troponin-T

ULN or BNP >100 pg/mL are eligible but must have cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy.

  1. Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within 28 days of Day 1 dosing with the following exceptions:
  1. Arm A: A minimum 5-day washout after discontinuation of ibrutinib therapy (or other BTK inhibitors) is required; only those subjects without rapid disease progression during the 5-day washout will be allowed to enroll into Arm A.

  2. Rapid disease progression is defined as follows:

  1. For subjects with measurable nodal disease, the increase in the sum of diameters of the largest lymph nodes (up to 3 nodes) exceeds

1 cm per day OR the diameter of the largest lymph node exceeds 5 cm during the 5 day wash out. 2. For subjects with lymphocytosis, the increase in the ALC exceeds 2x109/L per day OR the ALC exceeds 100,000 x109/L during the 5-day wash out; b. Arm C: No minimum washout is required after discontinuation of ibrutinib (or other BTK inhibitors) c. Approved PI3 kinase inhibitors: Subjects may start study treatment within 3 days of discontinuation of approved PI3 kinase inhibitors.

  1. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management

  2. Active disease transformation (ie, Richter's Syndrome); subjects with Richter's Syndrome that has resolved > 2 years from signing the ICD are eligible.

  3. Known acute or chronic pancreatitis 17. Pregnant or lactating females

Arm B only (CC-122 in combination with ibrutinib):
  1. Prior treatment with a BTK inhibitor 19. Presence of transfusion-dependent thrombocytopenia or a history of bleeding disorders or clinical conditions (eg, gastrointestinal bleeding or constitutional disorders) that may increase risk of life-threatening bleeding when thrombocytopenic 20. History of stroke or intracranial hemorrhage within 6 months prior to signing the ICD 21. Medications that are strong inhibitors or inducers of CYP3A4/5 (eg, itraconazole, ketoconazole, clarithromycin, ritonavir, phenytoin, pentobarbital, and rifampin) should be changed; subjects who cannot change these medications must be excluded.

  2. Use of concomitant anticoagulation with warfarin or other vitamin K antagonists is prohibited, as is treatment with these agents in the 7 days prior to signing the ICD. The use of other anticoagulants (eg, heparins) and anti-platelet agents is allowed per investigator's discretion.

Arm C only (CC-122 in combination with obinutuzumab):
  1. Hypersensitivity to obinutuzumab

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of California San DiegoLa JollaCaliforniaUnited States92093
2Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
3Hackensack University Medical CenterHackensackNew JerseyUnited States07601
4Weill Cornell Medical College Dr. Feldman's OfficeNew YorkNew YorkUnited States10065
5Ohio State University Medical CenterJames Cancer HospitalColumbusOhioUnited States43210
6The West ClinicMemphisTennesseeUnited States38120
7MD Anderson Cancer Center The University of TexasHoustonTexasUnited States77030
8Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98118
9University Hospital InnsbruckInnsbruckAustria6020
10University Hospital of Salzburg St Johanns SpitalSalzburgAustria5020
11Allgemeines Krankenhaus WienWienAustria1090
12Universitaetsklinikum EssenInnere Klinik und PoliklinikEssenGermany45147
13University of Schleswig-HolsteinKielGermany24116
14Universitat zu KolnKölnGermany50937
15Universitatsklinikum WürzburgWürzburgGermany97080
16Fondazione Centro San Raffaele del Monte TaborMilanoItaly20132
17Ospedale Niguarda MilanoMilanoItaly20162
18Arcispedale Santa Maria NuovaReggio EmiliaItaly42100
19Istituto Clinico HumanitasRozzano (MI)Italy20089
20Hospital Universitario Vall D hebronBarcelonaSpain08035
21Fundacion Jimenez DaazMadridSpain28040
22Hospital Universitario 12 de OctubreMadridSpain28041
23Hospital Universitario de SalamancaSalamancaSpain37007
24Hospital Universitario Virgen Del RocioSevillaSpain41013

Sponsors and Collaborators

  • Celgene

Investigators

  • Study Director: Vijaya Kesanakurthy, MD, Celgene

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT02406742
Other Study ID Numbers:
  • CC-122-CLL-001
First Posted:
Apr 2, 2015
Last Update Posted:
Sep 20, 2021
Last Verified:
Aug 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail46 participants treated
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Period Title: Overall Study
STARTED141616
Dose Escalation 1300
Dose Escalation 2953
Dose Escalation 3233
Dose Escalation 4033
Dose Escalation 5055
COMPLETED000
NOT COMPLETED141616

Baseline Characteristics

Arm/Group TitleArm AArm BArm CTotal
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose EscalationTotal of all reporting groups
Overall Participants14161646
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
67.4
(9.41)
63.4
(9.98)
61.5
(6.11)
64.0
(8.78)
Sex: Female, Male (Count of Participants)
Female
4
28.6%
8
50%
2
12.5%
14
30.4%
Male
10
71.4%
8
50%
14
87.5%
32
69.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
1
6.3%
0
0%
1
2.2%
Not Hispanic or Latino
14
100%
15
93.8%
16
100%
45
97.8%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
1
7.1%
0
0%
0
0%
1
2.2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
1
7.1%
0
0%
1
6.3%
2
4.3%
White
12
85.7%
16
100%
14
87.5%
42
91.3%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
1
6.3%
1
2.2%

Outcome Measures

1. Primary Outcome
TitleNumber of Participants and Severity of AEs
DescriptionNumber and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants141616
Grade 3 AE
8
8
9
Grade 4 AE
3
5
7
DLTs
0
0
0
2. Primary Outcome
TitleDetermination of Non Tolerated Dose (NTD) and Maximum Tolerated Dose (MTD)
DescriptionDetermination of the NTD and MTD in CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab
Time Frame52 weeks

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants01616
NTD
NA
NA
MTD
NA
NA
3. Secondary Outcome
TitleCC-122 Plasma Concentrations When Administered Alone or in Combination With Ibrutinib or Obinutuzumab
DescriptionCC-122 plasma concentrations when administered alone or in combination with ibrutinib or obinutuzumab
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
PK Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants1475
Geometric Mean (Geometric Coefficient of Variation) [Percentage]
NA
(NA)
NA
(NA)
NA
(NA)
4. Secondary Outcome
TitleIbrutinib Plasma Concentrations When Administered in Combination With CC-122
DescriptionGeometric mean concentration of Ibrutinib when administered alone or in combination with CC-122
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
PK Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants1475
Geometric Mean (Geometric Coefficient of Variation) [Percentage]
NA
(NA)
NA
(NA)
NA
(NA)
5. Secondary Outcome
TitleBest Overall Response (BOR)
DescriptionBest overall response [CR, CRi, nPR, PR, PRL (applicable to Arm B only)] CR = Complete Response CRi = Complete response with incomplete marrow recovery nPR = nodular Partial Response PR = Partial response PRL= Partial response with lymphocytosis
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants141616
Number (95% Confidence Interval) [Percentage]
7.1
87.5
62.5
6. Secondary Outcome
TitleMinimal Residual Disease Response Rate
DescriptionMinimal Residual Disease Response Rate in bone marrow and peripheral blood
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants141616
Bone Marrow
0
0
0
Peripheral Blood
0
0
18.8
7. Secondary Outcome
TitleDuration of Response
Descriptionmeasured from the time the response is first met until the first date that progressive disease or death is documented. Participants who neither progress nor die or who withdrew consent or are lost to follow-up prior to documentation of progression will be censored at the date of their last adequate response assessment.
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Safety population with Tumor response
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants11410
Median (95% Confidence Interval) [Days]
113
NA
602.0
8. Secondary Outcome
TitleProgression Free Survival (PFS)
Descriptionwill be calculated as the time from irst IP (i.e. any study drug) dose date to the first documented progression or death due to any cause during or after the treatment period, whichever occurs first.
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants141616
Median (95% Confidence Interval) [Months]
6.47
NA
22.57
9. Secondary Outcome
TitleCmax When Administered Alone or in Combination With Ibrutinib
DescriptionPeak (maximum) drug plasma concentration
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Intensive PK Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants500
Mean (95% Confidence Interval) [mg/mL]
NA
10. Secondary Outcome
TitleTmax of CC-122 When Administered Alone or in Combination With Ibrutinib
DescriptionTime to peak (maximum) drug concentration
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Intensive PK Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants500
Mean (95% Confidence Interval) [hours]
NA
11. Secondary Outcome
TitleAUC of CC-122 When Administered Alone or in Combination With Ibrutinib
DescriptionArea under the concentration -time curve calculated to the last observable concentration at time t
Time FrameApproximately 60 Months

Outcome Measure Data

Analysis Population Description
Intensive PK Population
Arm/Group TitleArm AArm BArm C
Arm/Group DescriptionCC-122 single agent Dose EscalationCC-122 in combination with ibrutinib Dose EscalationCC-122 in combination with obinutuzumab Dose Escalation
Measure Participants500
Mean (95% Confidence Interval) [Percentage]
NA

Adverse Events

Time FrameApproximately 60 Months
Adverse Event Reporting Description
Arm/Group TitleA (CC-122)B (CC-122+Ibrutinib)C (CC-122+Obinutuzumab)
Arm/Group DescriptionCC-122 single agentCC-122 in combination with ibrutinibCC-122 in combination with obinutuzumab
All Cause Mortality
A (CC-122)B (CC-122+Ibrutinib)C (CC-122+Obinutuzumab)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total2/14 (14.3%) 0/16 (0%) 1/16 (6.3%)
Serious Adverse Events
A (CC-122)B (CC-122+Ibrutinib)C (CC-122+Obinutuzumab)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total7/14 (50%) 7/16 (43.8%) 4/16 (25%)
Blood and lymphatic system disorders
Febrile neutropenia0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Haemolytic anaemia2/14 (14.3%) 0/16 (0%) 0/16 (0%)
Gastrointestinal disorders
Diarrhoea0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Stomatitis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Vomiting0/14 (0%) 1/16 (6.3%) 0/16 (0%)
General disorders
Pyrexia1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Infections and infestations
Bacteraemia1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Candida sepsis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Enterococcal sepsis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Influenza0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Pneumonia3/14 (21.4%) 2/16 (12.5%) 0/16 (0%)
Sepsis0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Urinary tract infection0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Injury, poisoning and procedural complications
Comminuted fracture0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Investigations
Troponin increased1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Metabolism and nutrition disorders
Tumour lysis syndrome0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Back pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Nervous system disorders
Cerebral artery occlusion0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Ischaemic stroke0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Syncope0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Other (Not Including Serious) Adverse Events
A (CC-122)B (CC-122+Ibrutinib)C (CC-122+Obinutuzumab)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total14/14 (100%) 16/16 (100%) 16/16 (100%)
Blood and lymphatic system disorders
Anaemia8/14 (57.1%) 0/16 (0%) 4/16 (25%)
Autoimmune haemolytic anaemia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Haemorrhagic disorder0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Leukocytosis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Leukopenia0/14 (0%) 0/16 (0%) 5/16 (31.3%)
Lymph node pain1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Lymphadenopathy0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Lymphocytosis0/14 (0%) 3/16 (18.8%) 4/16 (25%)
Lymphopenia0/14 (0%) 1/16 (6.3%) 7/16 (43.8%)
Neutropenia5/14 (35.7%) 6/16 (37.5%) 13/16 (81.3%)
Splenomegaly0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Thrombocytopenia2/14 (14.3%) 2/16 (12.5%) 6/16 (37.5%)
Cardiac disorders
Atrial fibrillation1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Bradycardia0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Bundle branch block right0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Cardiac valve disease0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Palpitations0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Sinus bradycardia1/14 (7.1%) 4/16 (25%) 1/16 (6.3%)
Sinus tachycardia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Tachycardia0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Tricuspid valve incompetence1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Ventricular hypertrophy0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Ear and labyrinth disorders
Autophony0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Ear discomfort0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Ear disorder0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Ear pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Hypoacusis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Tinnitus0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Vertigo1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Endocrine disorders
Hypothyroidism0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Eye disorders
Cataract1/14 (7.1%) 2/16 (12.5%) 0/16 (0%)
Chalazion0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Conjunctival haemorrhage1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Conjunctivitis allergic0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Diplopia0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Dry eye0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Dyschromatopsia0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Eye haemorrhage0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Eye irritation0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Eye pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Foreign body sensation in eyes0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Macular degeneration0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Maculopathy0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Meibomian gland dysfunction0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Photophobia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Photopsia0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Vision blurred0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Visual impairment0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Gastrointestinal disorders
Abdominal pain1/14 (7.1%) 4/16 (25%) 1/16 (6.3%)
Abdominal pain lower0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Abdominal pain upper1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Angular cheilitis0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Constipation2/14 (14.3%) 4/16 (25%) 2/16 (12.5%)
Dental caries0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Diarrhoea3/14 (21.4%) 7/16 (43.8%) 4/16 (25%)
Dry mouth0/14 (0%) 2/16 (12.5%) 2/16 (12.5%)
Dyspepsia0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Dysphagia0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Flatulence1/14 (7.1%) 0/16 (0%) 1/16 (6.3%)
Gastritis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Gastrointestinal polyp0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Gastrooesophageal reflux disease0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Gingival bleeding0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Inguinal hernia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Large intestine polyp0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Nausea1/14 (7.1%) 7/16 (43.8%) 5/16 (31.3%)
Noninfective gingivitis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Oral mucosal erythema1/14 (7.1%) 1/16 (6.3%) 0/16 (0%)
Oral pain0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Paraesthesia oral0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Stomatitis0/14 (0%) 7/16 (43.8%) 1/16 (6.3%)
Toothache0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Umbilical hernia1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Vomiting1/14 (7.1%) 3/16 (18.8%) 2/16 (12.5%)
General disorders
Asthenia3/14 (21.4%) 1/16 (6.3%) 0/16 (0%)
Catheter site bruise0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Chest pain0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Chills0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Fatigue3/14 (21.4%) 1/16 (6.3%) 5/16 (31.3%)
Feeling hot1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Influenza like illness0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Injection site pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Malaise0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Non-cardiac chest pain1/14 (7.1%) 3/16 (18.8%) 1/16 (6.3%)
Oedema peripheral3/14 (21.4%) 7/16 (43.8%) 3/16 (18.8%)
Pain0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Peripheral swelling0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Pyrexia5/14 (35.7%) 4/16 (25%) 3/16 (18.8%)
Immune system disorders
Cytokine release syndrome0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Seasonal allergy0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Infections and infestations
Arthritis infective0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Bacteraemia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Balanitis candida0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Body tinea0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Bronchitis0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Cellulitis0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Conjunctivitis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Cystitis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Diverticulitis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Fungal balanitis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Gingivitis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Haematoma infection0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Infection1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Influenza0/14 (0%) 3/16 (18.8%) 0/16 (0%)
Nasal herpes0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Nasopharyngitis1/14 (7.1%) 4/16 (25%) 5/16 (31.3%)
Oral candidiasis1/14 (7.1%) 1/16 (6.3%) 1/16 (6.3%)
Oral herpes0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Pharyngitis0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Pneumonia1/14 (7.1%) 2/16 (12.5%) 1/16 (6.3%)
Pseudomonal sepsis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Respiratory tract infection0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Rhinitis0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Sinusitis0/14 (0%) 1/16 (6.3%) 3/16 (18.8%)
Skin infection0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Tinea cruris0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Tinea infection0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Tonsillitis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Tooth abscess0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Tooth infection0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Upper respiratory tract infection1/14 (7.1%) 6/16 (37.5%) 5/16 (31.3%)
Urinary tract infection0/14 (0%) 3/16 (18.8%) 4/16 (25%)
Viral upper respiratory tract infection0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Vulvovaginal mycotic infection0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Wound infection0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Injury, poisoning and procedural complications
Arthropod bite0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Arthropod sting0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Buttock injury0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Comminuted fracture0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Contusion0/14 (0%) 4/16 (25%) 0/16 (0%)
Dental restoration failure0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Fall0/14 (0%) 6/16 (37.5%) 2/16 (12.5%)
Infusion related reaction0/14 (0%) 0/16 (0%) 7/16 (43.8%)
Ligament sprain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Limb injury0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Meniscus injury0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Muscle strain0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Post-traumatic neck syndrome0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Procedural nausea0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Procedural pain1/14 (7.1%) 0/16 (0%) 1/16 (6.3%)
Rib fracture0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Skin abrasion0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Skin laceration0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Spinal fracture0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Subcutaneous haematoma0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Thermal burn0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Tooth fracture0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Urinary retention postoperative0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Investigations
Alanine aminotransferase increased1/14 (7.1%) 1/16 (6.3%) 0/16 (0%)
Amylase increased1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Aspartate aminotransferase increased1/14 (7.1%) 1/16 (6.3%) 0/16 (0%)
Blood bilirubin increased0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Blood creatine phosphokinase increased2/14 (14.3%) 0/16 (0%) 0/16 (0%)
Blood creatinine increased1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Brain natriuretic peptide increased0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Electrocardiogram QT prolonged0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Hepatic enzyme increased1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Lipase increased1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Occult blood positive0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Weight decreased0/14 (0%) 2/16 (12.5%) 4/16 (25%)
Weight increased0/14 (0%) 6/16 (37.5%) 1/16 (6.3%)
Metabolism and nutrition disorders
Decreased appetite1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Dehydration0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Diabetes mellitus0/14 (0%) 3/16 (18.8%) 1/16 (6.3%)
Folate deficiency1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Gout0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Hypercalcaemia0/14 (0%) 0/16 (0%) 2/16 (12.5%)
Hyperglycaemia0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Hyperkalaemia1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Hyperphosphataemia1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Hyperuricaemia1/14 (7.1%) 1/16 (6.3%) 2/16 (12.5%)
Hypocalcaemia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Hypokalaemia0/14 (0%) 2/16 (12.5%) 2/16 (12.5%)
Hypomagnesaemia0/14 (0%) 0/16 (0%) 2/16 (12.5%)
Hypophosphataemia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Iron deficiency1/14 (7.1%) 2/16 (12.5%) 3/16 (18.8%)
Polydipsia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia2/14 (14.3%) 5/16 (31.3%) 2/16 (12.5%)
Back pain1/14 (7.1%) 4/16 (25%) 4/16 (25%)
Flank pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Joint swelling1/14 (7.1%) 0/16 (0%) 1/16 (6.3%)
Muscle contracture1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Muscle spasms1/14 (7.1%) 5/16 (31.3%) 4/16 (25%)
Muscular weakness0/14 (0%) 0/16 (0%) 2/16 (12.5%)
Musculoskeletal chest pain1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Musculoskeletal pain0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Myalgia2/14 (14.3%) 5/16 (31.3%) 2/16 (12.5%)
Neck pain0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Osteoporosis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Pain in extremity1/14 (7.1%) 2/16 (12.5%) 1/16 (6.3%)
Synovial cyst0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Benign neoplasm of skin0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Lipoma0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Lung adenocarcinoma0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Squamous cell carcinoma of skin0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Tumour flare2/14 (14.3%) 1/16 (6.3%) 1/16 (6.3%)
Nervous system disorders
Carotid arteriosclerosis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Carpal tunnel syndrome0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Cerebral artery occlusion0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Dizziness1/14 (7.1%) 5/16 (31.3%) 1/16 (6.3%)
Dizziness postural1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Headache3/14 (21.4%) 2/16 (12.5%) 2/16 (12.5%)
Memory impairment0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Paraesthesia0/14 (0%) 4/16 (25%) 2/16 (12.5%)
Peripheral sensory neuropathy0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Presyncope1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Speech disorder0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Syncope0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Tremor1/14 (7.1%) 2/16 (12.5%) 1/16 (6.3%)
Product Issues
Device occlusion0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Psychiatric disorders
Anxiety1/14 (7.1%) 1/16 (6.3%) 1/16 (6.3%)
Confusional state0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Depression0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Insomnia0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Irritability0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Libido decreased0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Mood altered0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Renal and urinary disorders
Dysuria0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Haematuria0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Nephrolithiasis0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Pollakiuria0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Strangury0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Urethral haemorrhage1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Urinary retention0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Urinary tract obstruction0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Erectile dysfunction0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Gynaecomastia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Nipple pain0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Vaginal haemorrhage0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Cough3/14 (21.4%) 5/16 (31.3%) 3/16 (18.8%)
Dyspnoea1/14 (7.1%) 1/16 (6.3%) 3/16 (18.8%)
Dyspnoea exertional0/14 (0%) 0/16 (0%) 2/16 (12.5%)
Epistaxis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Haemoptysis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Nasal congestion0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Oropharyngeal pain0/14 (0%) 8/16 (50%) 4/16 (25%)
Pleural effusion1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Productive cough0/14 (0%) 1/16 (6.3%) 2/16 (12.5%)
Pulmonary hypertension1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Pulmonary mass0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Pulmonary oedema1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Respiratory tract congestion1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Rhinalgia0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Rhinitis allergic0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Sinus congestion0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Skin and subcutaneous tissue disorders
Acne0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Actinic keratosis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Alopecia0/14 (0%) 2/16 (12.5%) 1/16 (6.3%)
Dermatitis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Dermatitis contact0/14 (0%) 1/16 (6.3%) 2/16 (12.5%)
Dry skin0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Ecchymosis1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Erythema0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Hair texture abnormal0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Hyperhidrosis1/14 (7.1%) 2/16 (12.5%) 2/16 (12.5%)
Hyperkeratosis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Nail discolouration0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Nail disorder0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Night sweats4/14 (28.6%) 3/16 (18.8%) 2/16 (12.5%)
Onychoclasis0/14 (0%) 3/16 (18.8%) 0/16 (0%)
Onychomadesis0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Petechiae0/14 (0%) 3/16 (18.8%) 1/16 (6.3%)
Precancerous skin lesion0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Pruritus1/14 (7.1%) 1/16 (6.3%) 3/16 (18.8%)
Rash1/14 (7.1%) 3/16 (18.8%) 2/16 (12.5%)
Rash erythematous1/14 (7.1%) 1/16 (6.3%) 0/16 (0%)
Rash macular0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Rash maculo-papular0/14 (0%) 3/16 (18.8%) 2/16 (12.5%)
Seborrhoeic dermatitis0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Skin haemorrhage0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Skin lesion0/14 (0%) 3/16 (18.8%) 2/16 (12.5%)
Skin mass0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Solar lentigo0/14 (0%) 1/16 (6.3%) 0/16 (0%)
Urticaria0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Vascular disorders
Deep vein thrombosis0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Flushing0/14 (0%) 0/16 (0%) 1/16 (6.3%)
Haematoma0/14 (0%) 2/16 (12.5%) 0/16 (0%)
Hot flush0/14 (0%) 1/16 (6.3%) 1/16 (6.3%)
Hypertension2/14 (14.3%) 6/16 (37.5%) 3/16 (18.8%)
Systolic hypertension1/14 (7.1%) 0/16 (0%) 0/16 (0%)
Thrombophlebitis superficial1/14 (7.1%) 0/16 (0%) 0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/TitleBristol-Myers Squibb Study Director
OrganizationBristol-Myers Squibb
PhonePlease Email
EmailClinical.Trials@bms.com
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT02406742
Other Study ID Numbers:
  • CC-122-CLL-001
First Posted:
Apr 2, 2015
Last Update Posted:
Sep 20, 2021
Last Verified:
Aug 1, 2021