Study of LY2835219 for Mantle Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT01739309
• Recruitment Status: Completed
• First Posted: December 3, 2012
• Results First Posted: February 15, 2019
• Last Update Posted: February 17, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mantle Cell Lymphoma
• Intervention: Drug: Abemaciclib
• Enrollment: 28

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Abemaciclib
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
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

Outcome Measures

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)
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable DCR data.

Arm/Group Title	Abemaciclib
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
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable BOR data.

Arm/Group Title	Abemaciclib
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)
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. 4 participants were censored.

Arm/Group Title	Abemaciclib
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)
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. 9 participants were censored.

Arm/Group Title	Abemaciclib
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)
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Abemaciclib
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
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Abemaciclib
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
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. 17 participants were censored.

Arm/Group Title	Abemaciclib
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
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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. 5 participants were censored.

Arm/Group Title	Abemaciclib
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
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)

Outcome Measure Data

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
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
Description	[Not Specified]
Time Frame	Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Abemaciclib
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
Description	[Not Specified]
Time Frame	Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Outcome Measure Data

Analysis Population Description

All randomized who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Abemaciclib
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
Description	[Not Specified]
Time Frame	Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Outcome Measure Data

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
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
Description	[Not Specified]
Time Frame	Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. Vd was not calculated by non-compartmental analysis with the available data.

Arm/Group Title	Abemaciclib
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
Description	[Not Specified]
Time Frame	Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Outcome Measure Data

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
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.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Abemaciclib
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	--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01739309
• 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: February 17, 2023