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Study of LY2835219 for Mantle Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT01739309
Recruitment Status : Active, not recruiting
First Posted : December 3, 2012
Results First Posted : February 15, 2019
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mantle Cell Lymphoma
Intervention Drug: Abemaciclib
Enrollment 28
Recruitment Details  
Pre-assignment Details Completers are those who died, or are alive and being followed at the end of the trial but off treatment.
Arm/Group Title Abemaciclib
Hide Arm/Group Description 200 milligram (mg) of Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Period Title: Overall Study
Started 28
Received at Least One Dose of Study Drug 28
Death Due to Any Cause 17
Alive and on Study, Off Treatment 8
Completed 25
Not Completed 3
Reason Not Completed
On study treatment             3
Arm/Group Title Abemaciclib
Hide Arm/Group Description 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants
68.4  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female 11
Male 17
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Hispanic or Latino 0
Not Hispanic or Latino 28
Unknown or Not Reported 0
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
American Indian or Alaska Native 0
Asian 0
Native Hawaiian or Other Pacific Islander 0
Black or African American 0
White 27
More than one race 0
Unknown or Not Reported 1
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
France 13
Germany 15
1.Primary Outcome
Title Percentage of Participants Who Achieve Disease Control Rate (DCR) Which Includes Complete Response (CR), Complete Response Unconfirmed (CRu), Partial Response (PR) or Stable Disease (SD)
Hide Description The DCR was estimated based on the Response Criteria for Non-Hodgkin’s Lymphomas (Cheson et al. 1999). DCR was assessed from date of first dose until disease progression or death or start of new anticancer therapy. CR is defined as the disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms based on CT scan or bone marrow biopsy; CRu = the CR criteria is met and a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the product diameter (SPD). PR is >= 50% decrease in SPD of the six largest nodal masses/no new sites of disease. Progressive Disease (PD) is defined as an increase by 25% in longest diameter, new lesion or assessable disease progression. SD=small changes not meeting the above criteria; DCR and its exact 95% CI was estimated for treated participants using the Clopper-Pearson method.
Time Frame From Date of First Dose until Disease Progression or Death or Start of New Anticancer Therapy (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable DCR data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
71.4
(51.3 to 86.8)
2.Secondary Outcome
Title Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR
Hide Description BOR was assessed based on the Response Criteria for Non-Hodgkin’s Lymphomas and was measured from date of first dose until the earliest evidence of objective progression or start of new anticancer therapy. Any responses observed after objective progression or after the start of new anticancer therapy are excluded from the determination of best response. A second confirmatory radiological tumor assessment was performed at least 28 days after the first evidence of response (CR, CRu, or PR). Two objective status determinations of CR (or CRu) before progression were required for a best response of CR (or CRu). Two determinations of PR or better before progression, but not qualifying for CR or CRu, were required for a best response of PR.
Time Frame From Date of First Dose until Disease Progression (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable BOR data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
35.7
(18.6 to 55.9)
3.Secondary Outcome
Title Duration of Objective Response (DOR)
Hide Description DOR is from the date when criteria for objective response (ie, CR, CRu or PR) are met, to the first documentation of relapse or disease progression or death due to any cause. DOR is based on the Response Criteria for Non-Hodgkin's Lymphomas of the Cancer and Leukemia Group B. CR is defined as disappearance of all disease, no symptoms and must last 4 weeks or "unconfirmed CR, (CRu)". PR is defined as >= 50% decrease in sum of product diameter (SPD), no increase or new lesion, or assessable disease stable or decreased, must last 4 weeks or CRu. Progressive Disease or PD is defined as an increase by 25% in longest diameter, new lesion, or assessable disease progression. DOR was analyzed using Kaplan-Meier methods. If the participant receives other anticancer therapy prior to progression, the participant was censored at the start date of this other therapy.
Time Frame From Date of CR, CRu or PR until Disease Progression or Death Due to Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. 4 participants were censored.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: months
12.39 [1] 
(3.19 to NA)
[1]
The upper limit of the 95% CI was not calculated due to the high censoring rate.
4.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS is defined as the date of first dose until disease progression or death due to any cause based on the Response Criteria for Non-Hodgkin’s Lymphomas. Disease progression is defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date after radiologic assessment has been completed. PD is defined as an increase by 25% in longest diameter, new lesion, or assessable disease progression. Progression-free survival was analyzed using Kaplan-Meier methods. If the participant receives other anticancer therapy prior to progression, the participant was censored at the start date of this other therapy.
Time Frame From Date of First Dose until Disease Progression or Death Due to Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. 9 participants were censored.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
8.18
(4.34 to 16.03)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as from the date of first dose until death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS were censored on the last date the participant is known to be alive. Overall survival was analyzed using Kaplan-Meier methods.
Time Frame From Date of First Dose until Death Due to Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
16.03 [1] 
(6.77 to NA)
[1]
The 95% confidence interval upper limit was not reached (NR).
6.Secondary Outcome
Title Event-Free Survival
Hide Description Event-free survival (time to treatment failure) is measured from date of first dose to disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, participant preference, initiation of new treatment without documented progression, or death due to any cause). 2 participants were censored. Event-free survival is defined only for responders (participants with a CR, CRu, or PR).
Time Frame From Date of First Dose until Disease Progression, Discontinuation of Treatment, or Death Due to Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg was Abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
11.29
(5.45 to 16.26)
7.Secondary Outcome
Title Time to Disease Progression
Hide Description Time to Disease Progression is based on the response criteria of Non-Hodgkin's Lymphomas. Time to progression (TTP) is defined as the time from date of first dose until documented disease progression or death as a result of lymphoma. In TTP, deaths from other causes are censored either at the time of death or at an earlier time of assessment.
Time Frame From Date of First Dose Until Disease Progression (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. 17 participants were censored.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
12.85 [1] 
(5.45 to NA)
[1]
The upper limit was not calculated due to the high censoring rate.
8.Secondary Outcome
Title Disease-Free Survival
Hide Description Disease-free survival is measured from first dose until date of disease progression or the time of occurrence of disease-free state or attainment of a CR to disease recurrence or death as a result of lymphoma or acute toxicity of treatment. Progressive Disease (PD) is defined as an increase by 25%, new lesion, or accessible progressive disease. Disease-Free Survival was assessed based on the response criteria of Non-Hodgkins Lymphomas. Disease-free survival is only defined for participants with response.
Time Frame First Dose Until Date of Disease Progression or Time of Occurrence Disease-Free State or CR to Disease Recurrence or Death (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. 5 participants were censored.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
9.20 [1] 
(3.19 to NA)
[1]
The 95% confidence interval upper limit was not reached (NR).
9.Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores
Hide Description Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population). The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes and lower scores indicate worse outcomes. A positive change from baseline indicates an improvement and a negative change is a detriment.
Time Frame Baseline, Cycle 5 (Up To Day 140)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had baseline and post baseline FACT-Lym data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Well-Being (PWB) Subscale Score 0.2  (5.6)
Functional (FWB) Subscale Score -0.9  (4.5)
LYM Subscale Score 1.1  (5.2)
FACT-Lym TOI Score 0.5  (12.5)
10.Secondary Outcome
Title Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
Hide Description [Not Specified]
Time Frame Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram/milliliter (ng/ml)
189
(59%)
11.Secondary Outcome
Title PK - Area Under the Concentration-Time Curve From Zero to Last Time Point (AUC[0-tlast]) of Abemaciclib
Hide Description [Not Specified]
Time Frame Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanogram/milliter (hr*ng/ml)
978
(61%)
12.Secondary Outcome
Title PK - Terminal Half Life (T 1/2) of Abemaciclib
Hide Description [Not Specified]
Time Frame Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the calculation of half-life (t1/2) by noncompartmental analysis was not possible due to cessation of sampling at 8 hours postdose.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title PK: Volume of Distribution (Vd) of Abemaciclib
Hide Description [Not Specified]
Time Frame Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed. Vd was not calculated by non-compartmental analysis with the available data.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title PK: Clearance (CL) of Abemaciclib
Hide Description [Not Specified]
Time Frame Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed. CL was not calculated due to PK sampling schedule was not suitable for estimation of these PK parameters.
Arm/Group Title Abemaciclib
Hide Arm/Group Description:
200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Abemaciclib
Hide Arm/Group Description 200 milligram (mg) Abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle
All-Cause Mortality
Abemaciclib
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Abemaciclib
Affected / at Risk (%) # Events
Total   12/28 (42.86%)    
Blood and lymphatic system disorders   
Anaemia  1  2/28 (7.14%)  2
Gastrointestinal disorders   
Nausea  1  1/28 (3.57%)  1
Rectal haemorrhage  1  1/28 (3.57%)  1
General disorders   
General physical health deterioration  1  1/28 (3.57%)  1
Pyrexia  1  1/28 (3.57%)  2
Infections and infestations   
Device related infection  1  1/28 (3.57%)  1
Lobar pneumonia  1  1/28 (3.57%)  1
Lung infection  1  1/28 (3.57%)  1
Meningitis  1  1/28 (3.57%)  1
Pneumonia  1  1/28 (3.57%)  1
Progressive multifocal leukoencephalopathy  1  1/28 (3.57%)  1
Sepsis  1  1/28 (3.57%)  1
Septic shock  1  1/28 (3.57%)  1
Injury, poisoning and procedural complications   
Fall  1  1/28 (3.57%)  1
Head injury  1  1/28 (3.57%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/28 (3.57%)  1
Nervous system disorders   
Nervous system disorder  1  1/28 (3.57%)  1
Somnolence  1  1/28 (3.57%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abemaciclib
Affected / at Risk (%) # Events
Total   28/28 (100.00%)    
Blood and lymphatic system disorders   
Anaemia  1  8/28 (28.57%)  8
Leukopenia  1  3/28 (10.71%)  5
Neutropenia  1  7/28 (25.00%)  8
Thrombocytopenia  1  11/28 (39.29%)  12
Gastrointestinal disorders   
Abdominal pain  1  4/28 (14.29%)  5
Diarrhoea  1  21/28 (75.00%)  31
Nausea  1  9/28 (32.14%)  14
Vomiting  1  8/28 (28.57%)  56
General disorders   
Asthenia  1  2/28 (7.14%)  3
Fatigue  1  10/28 (35.71%)  15
Oedema peripheral  1  6/28 (21.43%)  6
Pyrexia  1  4/28 (14.29%)  5
Infections and infestations   
Bronchitis  1  5/28 (17.86%)  5
Conjunctivitis  1  4/28 (14.29%)  4
Rhinitis  1  2/28 (7.14%)  2
Urinary tract infection  1  4/28 (14.29%)  6
Investigations   
Blood creatinine increased  1  7/28 (25.00%)  9
Neutrophil count decreased  1  4/28 (14.29%)  12
Platelet count decreased  1  3/28 (10.71%)  4
Weight decreased  1  2/28 (7.14%)  2
Metabolism and nutrition disorders   
Decreased appetite  1  4/28 (14.29%)  4
Hyperkalaemia  1  2/28 (7.14%)  2
Musculoskeletal and connective tissue disorders   
Muscle spasms  1  2/28 (7.14%)  2
Nervous system disorders   
Dizziness  1  4/28 (14.29%)  4
Dysgeusia  1  2/28 (7.14%)  2
Headache  1  2/28 (7.14%)  2
Presyncope  1  2/28 (7.14%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/28 (14.29%)  4
Dyspnoea  1  5/28 (17.86%)  5
Skin and subcutaneous tissue disorders   
Alopecia  1  3/28 (10.71%)  3
Night sweats  1  2/28 (7.14%)  3
Pruritus  1  3/28 (10.71%)  3
Vascular disorders   
Hypotension  1  2/28 (7.14%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01739309     History of Changes
Other Study ID Numbers: 13269
I3Y-MC-JPBB ( Other Identifier: Eli Lilly and Company )
2012-003614-14 ( EudraCT Number )
First Submitted: November 29, 2012
First Posted: December 3, 2012
Results First Submitted: October 27, 2017
Results First Posted: February 15, 2019
Last Update Posted: September 25, 2019