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
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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
Arms and Interventions
| Arm | Intervention/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
- 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
- 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
- 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
- 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
- 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
- Minimal Residual Disease Response Rate [Approximately 60 Months]
Minimal Residual Disease Response Rate in bone marrow and peripheral blood
- 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.
- 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.
- Cmax When Administered Alone or in Combination With Ibrutinib [Approximately 60 Months]
Peak (maximum) drug plasma concentration
- Tmax of CC-122 When Administered Alone or in Combination With Ibrutinib [Approximately 60 Months]
Time to peak (maximum) drug concentration
- 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
Inclusion Criteria:
-
Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed consent form.
-
Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
-
Able to adhere to the study visit schedule and other protocol requirements.
-
Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL guidelines). In addition:
- 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:
- 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;
-
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:
-
has 17p- and/or TP53 mutation; or
-
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.
-
Subjects must have the following lab values:
-
Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to bone marrow involvement by disease.
-
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.
-
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x upper limit of normal (ULN) unless due to disease.
-
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)
-
Calculated creatinine clearance of ≥ 60 ml/min.
-
No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
-
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:
-
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.
-
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.
-
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.
-
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.
-
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.
-
Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn.
-
Be counseled about pregnancy precautions and risks of fetal exposure.
ARM B ONLY:
- 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:
-
Subjects in Cohort 2 of Arm C must meet the following criteria:
-
Subject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax;
-
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:
- 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:
-
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:
-
Ongoing or active infection requiring parenteral antibiotics.
-
Uncontrolled diabetes mellitus.
-
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.
-
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 or requirement of therapy that would confound study results. This does not 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.
-
Carcinoma in situ of the bladder.
-
Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).
-
Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV), or hepatitis B or C virus (HBV, HCV).
- 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.
-
Any peripheral neuropathy ≥ NCI CTCAE Grade 2.
-
Use of systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day.
-
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.
-
History of hypersensitivity to IMiDs® (lenalidomide, pomalidomide, thalidomide).
-
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
-
Left ventricular ejection fraction (LVEF) < 45% as determined by MUGA scan or echocardiogram (ECHO).
-
Complete left bundle branch, or bifasicular, block.
-
Congenital long QT syndrome.
-
Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation.
-
QTcF > 470 msec on Screening ECG (mean of triplicate recordings).
-
Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC
-
Uncontrolled congestive heart failure or uncontrolled hypertension.
-
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.
- Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within 28 days of Day 1 dosing with the following exceptions:
-
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.
-
Rapid disease progression is defined as follows:
- 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.
-
Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management
-
Active disease transformation (ie, Richter's Syndrome); subjects with Richter's Syndrome that has resolved > 2 years from signing the ICD are eligible.
-
Known acute or chronic pancreatitis 17. Pregnant or lactating females
Arm B only (CC-122 in combination with ibrutinib):
-
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.
-
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):
- Hypersensitivity to obinutuzumab
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Diego | La Jolla | California | United States | 92093 |
| 2 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 3 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 4 | Weill Cornell Medical College Dr. Feldman's Office | New York | New York | United States | 10065 |
| 5 | Ohio State University Medical CenterJames Cancer Hospital | Columbus | Ohio | United States | 43210 |
| 6 | The West Clinic | Memphis | Tennessee | United States | 38120 |
| 7 | MD Anderson Cancer Center The University of Texas | Houston | Texas | United States | 77030 |
| 8 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98118 |
| 9 | University Hospital Innsbruck | Innsbruck | Austria | 6020 | |
| 10 | University Hospital of Salzburg St Johanns Spital | Salzburg | Austria | 5020 | |
| 11 | Allgemeines Krankenhaus Wien | Wien | Austria | 1090 | |
| 12 | Universitaetsklinikum EssenInnere Klinik und Poliklinik | Essen | Germany | 45147 | |
| 13 | University of Schleswig-Holstein | Kiel | Germany | 24116 | |
| 14 | Universitat zu Koln | Köln | Germany | 50937 | |
| 15 | Universitatsklinikum Würzburg | Würzburg | Germany | 97080 | |
| 16 | Fondazione Centro San Raffaele del Monte Tabor | Milano | Italy | 20132 | |
| 17 | Ospedale Niguarda Milano | Milano | Italy | 20162 | |
| 18 | Arcispedale Santa Maria Nuova | Reggio Emilia | Italy | 42100 | |
| 19 | Istituto Clinico Humanitas | Rozzano (MI) | Italy | 20089 | |
| 20 | Hospital Universitario Vall D hebron | Barcelona | Spain | 08035 | |
| 21 | Fundacion Jimenez Daaz | Madrid | Spain | 28040 | |
| 22 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 23 | Hospital Universitario de Salamanca | Salamanca | Spain | 37007 | |
| 24 | Hospital Universitario Virgen Del Rocio | Sevilla | Spain | 41013 |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Vijaya Kesanakurthy, MD, Celgene
Study Documents (Full-Text)
More Information
Publications
None provided.- CC-122-CLL-001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 46 participants treated |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Period Title: Overall Study | |||
| STARTED | 14 | 16 | 16 |
| Dose Escalation 1 | 3 | 0 | 0 |
| Dose Escalation 2 | 9 | 5 | 3 |
| Dose Escalation 3 | 2 | 3 | 3 |
| Dose Escalation 4 | 0 | 3 | 3 |
| Dose Escalation 5 | 0 | 5 | 5 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 14 | 16 | 16 |
Baseline Characteristics
| Arm/Group Title | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation | Total of all reporting groups |
| Overall Participants | 14 | 16 | 16 | 46 |
| 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
| Title | Number of Participants and Severity of AEs |
|---|---|
| Description | Number and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 16 | 16 |
| Grade 3 AE |
8
|
8
|
9
|
| Grade 4 AE |
3
|
5
|
7
|
| DLTs |
0
|
0
|
0
|
| Title | Determination of Non Tolerated Dose (NTD) and Maximum Tolerated Dose (MTD) |
|---|---|
| Description | Determination of the NTD and MTD in CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 0 | 16 | 16 |
| NTD |
NA
|
NA
|
|
| MTD |
NA
|
NA
|
| Title | CC-122 Plasma Concentrations When Administered Alone or in Combination With Ibrutinib or Obinutuzumab |
|---|---|
| Description | CC-122 plasma concentrations when administered alone or in combination with ibrutinib or obinutuzumab |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 7 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage] |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Ibrutinib Plasma Concentrations When Administered in Combination With CC-122 |
|---|---|
| Description | Geometric mean concentration of Ibrutinib when administered alone or in combination with CC-122 |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 7 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage] |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Best Overall Response (BOR) |
|---|---|
| Description | 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 |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 16 | 16 |
| Number (95% Confidence Interval) [Percentage] |
7.1
|
87.5
|
62.5
|
| Title | Minimal Residual Disease Response Rate |
|---|---|
| Description | Minimal Residual Disease Response Rate in bone marrow and peripheral blood |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 16 | 16 |
| Bone Marrow |
0
|
0
|
0
|
| Peripheral Blood |
0
|
0
|
18.8
|
| Title | Duration of Response |
|---|---|
| Description | 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. |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population with Tumor response |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 1 | 14 | 10 |
| Median (95% Confidence Interval) [Days] |
113
|
NA
|
602.0
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 14 | 16 | 16 |
| Median (95% Confidence Interval) [Months] |
6.47
|
NA
|
22.57
|
| Title | Cmax When Administered Alone or in Combination With Ibrutinib |
|---|---|
| Description | Peak (maximum) drug plasma concentration |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intensive PK Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 5 | 0 | 0 |
| Mean (95% Confidence Interval) [mg/mL] |
NA
|
| Title | Tmax of CC-122 When Administered Alone or in Combination With Ibrutinib |
|---|---|
| Description | Time to peak (maximum) drug concentration |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intensive PK Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 5 | 0 | 0 |
| Mean (95% Confidence Interval) [hours] |
NA
|
| Title | AUC of CC-122 When Administered Alone or in Combination With Ibrutinib |
|---|---|
| Description | Area under the concentration -time curve calculated to the last observable concentration at time t |
| Time Frame | Approximately 60 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intensive PK Population |
| Arm/Group Title | Arm A | Arm B | Arm C |
|---|---|---|---|
| Arm/Group Description | CC-122 single agent Dose Escalation | CC-122 in combination with ibrutinib Dose Escalation | CC-122 in combination with obinutuzumab Dose Escalation |
| Measure Participants | 5 | 0 | 0 |
| Mean (95% Confidence Interval) [Percentage] |
NA
|
Adverse Events
| Time Frame | Approximately 60 Months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | A (CC-122) | B (CC-122+Ibrutinib) | C (CC-122+Obinutuzumab) | |||
| Arm/Group Description | CC-122 single agent | CC-122 in combination with ibrutinib | CC-122 in combination with obinutuzumab | |||
All Cause Mortality |
||||||
| A (CC-122) | B (CC-122+Ibrutinib) | C (CC-122+Obinutuzumab) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/14 (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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/14 (50%) | 7/16 (43.8%) | 4/16 (25%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Haemolytic anaemia | 2/14 (14.3%) | 0/16 (0%) | 0/16 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Stomatitis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Vomiting | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| General disorders | ||||||
| Pyrexia | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Infections and infestations | ||||||
| Bacteraemia | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Candida sepsis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Enterococcal sepsis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Influenza | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Pneumonia | 3/14 (21.4%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Sepsis | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Urinary tract infection | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Comminuted fracture | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Investigations | ||||||
| Troponin increased | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Tumour lysis syndrome | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Lung adenocarcinoma | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Nervous system disorders | ||||||
| Cerebral artery occlusion | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Ischaemic stroke | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Syncope | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis contact | 0/14 (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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/14 (100%) | 16/16 (100%) | 16/16 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 8/14 (57.1%) | 0/16 (0%) | 4/16 (25%) | |||
| Autoimmune haemolytic anaemia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Haemorrhagic disorder | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Leukocytosis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Leukopenia | 0/14 (0%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Lymph node pain | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Lymphadenopathy | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Lymphocytosis | 0/14 (0%) | 3/16 (18.8%) | 4/16 (25%) | |||
| Lymphopenia | 0/14 (0%) | 1/16 (6.3%) | 7/16 (43.8%) | |||
| Neutropenia | 5/14 (35.7%) | 6/16 (37.5%) | 13/16 (81.3%) | |||
| Splenomegaly | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Thrombocytopenia | 2/14 (14.3%) | 2/16 (12.5%) | 6/16 (37.5%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Bradycardia | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Bundle branch block right | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Cardiac valve disease | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Palpitations | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Sinus bradycardia | 1/14 (7.1%) | 4/16 (25%) | 1/16 (6.3%) | |||
| Sinus tachycardia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tachycardia | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Tricuspid valve incompetence | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Ventricular hypertrophy | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Autophony | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Ear discomfort | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Ear disorder | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Ear pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hypoacusis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Tinnitus | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Vertigo | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Endocrine disorders | ||||||
| Hypothyroidism | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Eye disorders | ||||||
| Cataract | 1/14 (7.1%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Chalazion | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Conjunctival haemorrhage | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Conjunctivitis allergic | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Diplopia | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Dry eye | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Dyschromatopsia | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Eye haemorrhage | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Eye irritation | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Eye pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Foreign body sensation in eyes | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Macular degeneration | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Maculopathy | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Meibomian gland dysfunction | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Photophobia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Photopsia | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Vision blurred | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Visual impairment | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/14 (7.1%) | 4/16 (25%) | 1/16 (6.3%) | |||
| Abdominal pain lower | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Abdominal pain upper | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Angular cheilitis | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Constipation | 2/14 (14.3%) | 4/16 (25%) | 2/16 (12.5%) | |||
| Dental caries | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Diarrhoea | 3/14 (21.4%) | 7/16 (43.8%) | 4/16 (25%) | |||
| Dry mouth | 0/14 (0%) | 2/16 (12.5%) | 2/16 (12.5%) | |||
| Dyspepsia | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Dysphagia | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Flatulence | 1/14 (7.1%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gastritis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Gastrointestinal polyp | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Gastrooesophageal reflux disease | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Gingival bleeding | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Inguinal hernia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Large intestine polyp | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Nausea | 1/14 (7.1%) | 7/16 (43.8%) | 5/16 (31.3%) | |||
| Noninfective gingivitis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Oral mucosal erythema | 1/14 (7.1%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Oral pain | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Paraesthesia oral | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Stomatitis | 0/14 (0%) | 7/16 (43.8%) | 1/16 (6.3%) | |||
| Toothache | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Umbilical hernia | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Vomiting | 1/14 (7.1%) | 3/16 (18.8%) | 2/16 (12.5%) | |||
| General disorders | ||||||
| Asthenia | 3/14 (21.4%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Catheter site bruise | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Chest pain | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Chills | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Fatigue | 3/14 (21.4%) | 1/16 (6.3%) | 5/16 (31.3%) | |||
| Feeling hot | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Influenza like illness | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Injection site pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Malaise | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Non-cardiac chest pain | 1/14 (7.1%) | 3/16 (18.8%) | 1/16 (6.3%) | |||
| Oedema peripheral | 3/14 (21.4%) | 7/16 (43.8%) | 3/16 (18.8%) | |||
| Pain | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Peripheral swelling | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pyrexia | 5/14 (35.7%) | 4/16 (25%) | 3/16 (18.8%) | |||
| Immune system disorders | ||||||
| Cytokine release syndrome | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Seasonal allergy | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Infections and infestations | ||||||
| Arthritis infective | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Bacteraemia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Balanitis candida | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Body tinea | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Bronchitis | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Cellulitis | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Conjunctivitis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Cystitis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Diverticulitis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Fungal balanitis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gingivitis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Haematoma infection | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Infection | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Influenza | 0/14 (0%) | 3/16 (18.8%) | 0/16 (0%) | |||
| Nasal herpes | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nasopharyngitis | 1/14 (7.1%) | 4/16 (25%) | 5/16 (31.3%) | |||
| Oral candidiasis | 1/14 (7.1%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Oral herpes | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pharyngitis | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Pneumonia | 1/14 (7.1%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Pseudomonal sepsis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Respiratory tract infection | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Rhinitis | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Sinusitis | 0/14 (0%) | 1/16 (6.3%) | 3/16 (18.8%) | |||
| Skin infection | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tinea cruris | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tinea infection | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Tonsillitis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tooth abscess | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Tooth infection | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Upper respiratory tract infection | 1/14 (7.1%) | 6/16 (37.5%) | 5/16 (31.3%) | |||
| Urinary tract infection | 0/14 (0%) | 3/16 (18.8%) | 4/16 (25%) | |||
| Viral upper respiratory tract infection | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Vulvovaginal mycotic infection | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Wound infection | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Arthropod sting | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Buttock injury | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Comminuted fracture | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Contusion | 0/14 (0%) | 4/16 (25%) | 0/16 (0%) | |||
| Dental restoration failure | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Fall | 0/14 (0%) | 6/16 (37.5%) | 2/16 (12.5%) | |||
| Infusion related reaction | 0/14 (0%) | 0/16 (0%) | 7/16 (43.8%) | |||
| Ligament sprain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Limb injury | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Meniscus injury | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Muscle strain | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Post-traumatic neck syndrome | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Procedural nausea | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Procedural pain | 1/14 (7.1%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Rib fracture | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Skin abrasion | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Skin laceration | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Spinal fracture | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Subcutaneous haematoma | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Thermal burn | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Tooth fracture | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Urinary retention postoperative | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/14 (7.1%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Amylase increased | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Aspartate aminotransferase increased | 1/14 (7.1%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Blood bilirubin increased | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Blood creatine phosphokinase increased | 2/14 (14.3%) | 0/16 (0%) | 0/16 (0%) | |||
| Blood creatinine increased | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Brain natriuretic peptide increased | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Electrocardiogram QT prolonged | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hepatic enzyme increased | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Lipase increased | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Occult blood positive | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Weight decreased | 0/14 (0%) | 2/16 (12.5%) | 4/16 (25%) | |||
| Weight increased | 0/14 (0%) | 6/16 (37.5%) | 1/16 (6.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Dehydration | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Diabetes mellitus | 0/14 (0%) | 3/16 (18.8%) | 1/16 (6.3%) | |||
| Folate deficiency | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Gout | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Hypercalcaemia | 0/14 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hyperglycaemia | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Hyperkalaemia | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Hyperphosphataemia | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Hyperuricaemia | 1/14 (7.1%) | 1/16 (6.3%) | 2/16 (12.5%) | |||
| Hypocalcaemia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hypokalaemia | 0/14 (0%) | 2/16 (12.5%) | 2/16 (12.5%) | |||
| Hypomagnesaemia | 0/14 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hypophosphataemia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Iron deficiency | 1/14 (7.1%) | 2/16 (12.5%) | 3/16 (18.8%) | |||
| Polydipsia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/14 (14.3%) | 5/16 (31.3%) | 2/16 (12.5%) | |||
| Back pain | 1/14 (7.1%) | 4/16 (25%) | 4/16 (25%) | |||
| Flank pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Joint swelling | 1/14 (7.1%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Muscle contracture | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Muscle spasms | 1/14 (7.1%) | 5/16 (31.3%) | 4/16 (25%) | |||
| Muscular weakness | 0/14 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Musculoskeletal chest pain | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Musculoskeletal pain | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Myalgia | 2/14 (14.3%) | 5/16 (31.3%) | 2/16 (12.5%) | |||
| Neck pain | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Osteoporosis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Pain in extremity | 1/14 (7.1%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Synovial cyst | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Benign neoplasm of skin | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Lipoma | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Lung adenocarcinoma | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Squamous cell carcinoma of skin | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tumour flare | 2/14 (14.3%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Nervous system disorders | ||||||
| Carotid arteriosclerosis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Carpal tunnel syndrome | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Cerebral artery occlusion | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Dizziness | 1/14 (7.1%) | 5/16 (31.3%) | 1/16 (6.3%) | |||
| Dizziness postural | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Headache | 3/14 (21.4%) | 2/16 (12.5%) | 2/16 (12.5%) | |||
| Memory impairment | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Paraesthesia | 0/14 (0%) | 4/16 (25%) | 2/16 (12.5%) | |||
| Peripheral sensory neuropathy | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Presyncope | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Speech disorder | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Syncope | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Tremor | 1/14 (7.1%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Product Issues | ||||||
| Device occlusion | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 1/14 (7.1%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Confusional state | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Depression | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Insomnia | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Irritability | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Libido decreased | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Mood altered | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Haematuria | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Nephrolithiasis | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Pollakiuria | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Strangury | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Urethral haemorrhage | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Urinary retention | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Urinary tract obstruction | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Erectile dysfunction | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Gynaecomastia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nipple pain | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Vaginal haemorrhage | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/14 (21.4%) | 5/16 (31.3%) | 3/16 (18.8%) | |||
| Dyspnoea | 1/14 (7.1%) | 1/16 (6.3%) | 3/16 (18.8%) | |||
| Dyspnoea exertional | 0/14 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Epistaxis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Haemoptysis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Nasal congestion | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Oropharyngeal pain | 0/14 (0%) | 8/16 (50%) | 4/16 (25%) | |||
| Pleural effusion | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Productive cough | 0/14 (0%) | 1/16 (6.3%) | 2/16 (12.5%) | |||
| Pulmonary hypertension | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Pulmonary mass | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pulmonary oedema | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Respiratory tract congestion | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Rhinalgia | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Rhinitis allergic | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Sinus congestion | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Actinic keratosis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Alopecia | 0/14 (0%) | 2/16 (12.5%) | 1/16 (6.3%) | |||
| Dermatitis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dermatitis contact | 0/14 (0%) | 1/16 (6.3%) | 2/16 (12.5%) | |||
| Dry skin | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Ecchymosis | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Erythema | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Hair texture abnormal | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Hyperhidrosis | 1/14 (7.1%) | 2/16 (12.5%) | 2/16 (12.5%) | |||
| Hyperkeratosis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Nail discolouration | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Nail disorder | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Night sweats | 4/14 (28.6%) | 3/16 (18.8%) | 2/16 (12.5%) | |||
| Onychoclasis | 0/14 (0%) | 3/16 (18.8%) | 0/16 (0%) | |||
| Onychomadesis | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Petechiae | 0/14 (0%) | 3/16 (18.8%) | 1/16 (6.3%) | |||
| Precancerous skin lesion | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Pruritus | 1/14 (7.1%) | 1/16 (6.3%) | 3/16 (18.8%) | |||
| Rash | 1/14 (7.1%) | 3/16 (18.8%) | 2/16 (12.5%) | |||
| Rash erythematous | 1/14 (7.1%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Rash macular | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Rash maculo-papular | 0/14 (0%) | 3/16 (18.8%) | 2/16 (12.5%) | |||
| Seborrhoeic dermatitis | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Skin haemorrhage | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Skin lesion | 0/14 (0%) | 3/16 (18.8%) | 2/16 (12.5%) | |||
| Skin mass | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Solar lentigo | 0/14 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Urticaria | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Flushing | 0/14 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Haematoma | 0/14 (0%) | 2/16 (12.5%) | 0/16 (0%) | |||
| Hot flush | 0/14 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Hypertension | 2/14 (14.3%) | 6/16 (37.5%) | 3/16 (18.8%) | |||
| Systolic hypertension | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
| Thrombophlebitis superficial | 1/14 (7.1%) | 0/16 (0%) | 0/16 (0%) | |||
Limitations/Caveats
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/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | Please Email |
| Clinical.Trials@bms.com |
- CC-122-CLL-001