Study of LY2835219 for Mantle Cell Lymphoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01739309
• Collaborator: (none)
• Enrollment: 28
• Locations: 7
• Arm: 1
• Anticipated Duration (Months): 120.5
• Patients Per Site: 4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to estimate the disease control rate with abemaciclib for relapsed or refractory mantle cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Drug: Abemaciclib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of a CDK4/6 Inhibitor for Patients With Relapsed or Refractory Mantle Cell Lymphoma
• Actual Study Start Date: Mar 20, 2013
• Actual Primary Completion Date: Sep 28, 2015
• Anticipated Study Completion Date: Apr 6, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abemaciclib 200 milligram (mg) abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle	Drug: Abemaciclib; Administered orally; Other Names: LY2835219

Outcome Measures

Primary Outcome Measures

1. 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) [From Date of First Dose until Disease Progression or Death or Start of New Anticancer Therapy (Up to 28 Months)]

   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.

Secondary Outcome Measures

1. Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR [From Date of First Dose until Disease Progression (Up to 28 Months)]

   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.

2. Duration of Objective Response (DOR) [From Date of CR, CRu or PR until Disease Progression or Death Due to Any Cause (Up to 28 Months)]

   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.

3. Progression-Free Survival (PFS) [From Date of First Dose until Disease Progression or Death Due to Any Cause (Up to 28 Months)]

   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.

4. Overall Survival (OS) [From Date of First Dose until Death Due to Any Cause (Up to 28 Months)]

   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.

5. Event-Free Survival [From Date of First Dose until Disease Progression, Discontinuation of Treatment, or Death Due to Any Cause (Up to 28 Months)]

   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).

6. Time to Disease Progression [From Date of First Dose Until Disease Progression (Up to 28 Months)]

   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.

7. Disease-Free Survival [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)]

   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.

8. Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores [Baseline, Cycle 5 (Up To Day 140)]

   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.

9. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib [Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose]

10. PK - Area Under the Concentration-Time Curve From Zero to Last Time Point (AUC[0-tlast]) of Abemaciclib [Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose]

11. PK - Terminal Half Life (T 1/2) of Abemaciclib [Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose]

12. PK: Volume of Distribution (Vd) of Abemaciclib [Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose]

13. PK: Clearance (CL) of Abemaciclib [Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of relapsed or refractory Mantle Cell Lymphoma (MCL) according to the World Health Organization (WHO) classification that has relapsed after, or been refractory to, available standard treatments. However, participants who are intolerant of, or unable to receive a standard treatment are not required to have MCL that has relapsed after, or been refractory to, that specific standard treatment. Pathology must be reviewed and confirmed at the investigational site where participant is entered prior to enrollment

• Have disease that is assessable according to the Response Criteria for Non- Hodgkin's Lymphomas

• Have given written informed consent prior to any study-specific procedures

• Have adequate organ function including:

• Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10^{9/Liter (L), platelets ≥75 x 10}9/L, and hemoglobin ≥8 grams per deciliter (g/dL)

• Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN) and alanine aminotransferase (ALT) ≤3.0 times ULN

• Renal: Estimated creatinine clearance ≥50 milliliter per minute (ml/min)

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia

• Are willing to make themselves available for the duration of the study and to follow study procedures

• Are amenable to compliance with protocol schedules and testing

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug

• Females with child-bearing potential must have a negative serum pregnancy test within 14 days of the first dose of study drug

• Have a life expectancy of ≥12 weeks

• Are able to swallow capsules

Exclusion Criteria:

• Are currently enrolled in, or discontinued within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively, a clinical trial involving an investigational product or non-approved use of a drug or device other than the study drug used in this study, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, pneumonia, inflammatory bowel disease, history of major surgical resection involving the stomach or small bowel)

• Have symptomatic metastasis to the central nervous system (CNS). Participants may have CNS metastasis that is radiographically or clinically stable for at least 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids

• Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogenic stemcell transplant must have discontinued immunosuppressive therapy at least 14 days before study drug administration with no more than Grade 1 acute graft versus-host disease on Day 1 of Cycle 1

• Females who are pregnant or lactating

• Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen [HBSAg], or hepatitis C antibodies). Screening is not required for enrollment

• Have a baseline electrocardiogram (ECG) with any of the following findings: ventricular tachycardia, ventricular fibrillation, abnormal QTcB (defined as ≥450 milliseconds for males and ≥470 milliseconds for females), or evidence of acute myocardial ischemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lille		France	59037
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pessac		France	33604
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Homburg		Germany	66421
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kassel		Germany	34125
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mainz		Germany	55131
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nürnberg		Germany	90419
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ulm		Germany	89081

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01739309
• Other Study ID Numbers: 13269; I3Y-MC-JPBB; 2012-003614-14
• First Posted: Dec 3, 2012
• Last Update Posted: Apr 27, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: Non- Hodgkins Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell

Study Results

Participant Flow

Pre-assignment Detail	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

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 Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (7.8)
Sex: Female, Male (Count of Participants)
Female	11 39.3%
Male	17 60.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	28 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	27 96.4%
More than one race	0 0%
Unknown or Not Reported	1 3.6%
Region of Enrollment (Count of Participants)
France	13 46.4%
Germany	15 53.6%

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.
Measure Participants	20
Number (95% Confidence Interval) [percentage of participants]	71.4 255%

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.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	35.7 127.5%

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
Measure Participants	28
Median (95% Confidence Interval) [months]	12.39

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.
Measure Participants	28
Median (95% Confidence Interval) [Months]	8.18

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.
Measure Participants	28
Median (95% Confidence Interval) [Months]	16.03

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.
Measure Participants	28
Median (95% Confidence Interval) [Months]	11.29

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.
Measure Participants	28
Median (95% Confidence Interval) [Months]	12.85

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.
Measure Participants	28
Median (95% Confidence Interval) [Months]	9.20

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.
Measure Participants	13
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
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.
Measure Participants	26
Geometric Mean (Geometric Coefficient of Variation) [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
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.
Measure Participants	26
Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram/milliter (hr*ng/ml)]	978 (61)

12. Secondary Outcome

Title	PK - Terminal Half Life (T 1/2) of Abemaciclib
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
Measure Participants	0

13. Secondary Outcome

Title	PK: Volume of Distribution (Vd) of Abemaciclib
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
Measure Participants	0

14. Secondary Outcome

Title	PK: Clearance (CL) of Abemaciclib
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.
Measure Participants	0

Adverse Events

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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Abemaciclib
	Affected / at Risk (%)	# Events
Total	12/28 (42.9%)
Blood and lymphatic system disorders
Anaemia	2/28 (7.1%)	2
Gastrointestinal disorders
Nausea	1/28 (3.6%)	1
Rectal haemorrhage	1/28 (3.6%)	1
General disorders
General physical health deterioration	1/28 (3.6%)	1
Pyrexia	1/28 (3.6%)	2
Infections and infestations
Device related infection	1/28 (3.6%)	1
Lobar pneumonia	1/28 (3.6%)	1
Lung infection	1/28 (3.6%)	1
Meningitis	1/28 (3.6%)	1
Pneumonia	1/28 (3.6%)	1
Progressive multifocal leukoencephalopathy	1/28 (3.6%)	1
Sepsis	1/28 (3.6%)	1
Septic shock	1/28 (3.6%)	1
Injury, poisoning and procedural complications
Fall	1/28 (3.6%)	1
Head injury	1/28 (3.6%)	1
Metabolism and nutrition disorders
Dehydration	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/28 (3.6%)	1
Nervous system disorders
Nervous system disorder	1/28 (3.6%)	1
Somnolence	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Abemaciclib
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Anaemia	8/28 (28.6%)	8
Leukopenia	3/28 (10.7%)	5
Neutropenia	7/28 (25%)	8
Thrombocytopenia	11/28 (39.3%)	12
Gastrointestinal disorders
Abdominal pain	4/28 (14.3%)	5
Diarrhoea	21/28 (75%)	31
Nausea	9/28 (32.1%)	14
Vomiting	8/28 (28.6%)	56
General disorders
Asthenia	2/28 (7.1%)	3
Fatigue	10/28 (35.7%)	15
Oedema peripheral	6/28 (21.4%)	6
Pyrexia	4/28 (14.3%)	5
Infections and infestations
Bronchitis	5/28 (17.9%)	5
Conjunctivitis	4/28 (14.3%)	4
Rhinitis	2/28 (7.1%)	2
Urinary tract infection	4/28 (14.3%)	6
Investigations
Blood creatinine increased	7/28 (25%)	9
Neutrophil count decreased	4/28 (14.3%)	12
Platelet count decreased	3/28 (10.7%)	4
Weight decreased	2/28 (7.1%)	2
Metabolism and nutrition disorders
Decreased appetite	4/28 (14.3%)	4
Hyperkalaemia	2/28 (7.1%)	2
Musculoskeletal and connective tissue disorders
Muscle spasms	2/28 (7.1%)	2
Nervous system disorders
Dizziness	4/28 (14.3%)	4
Dysgeusia	2/28 (7.1%)	2
Headache	2/28 (7.1%)	2
Presyncope	2/28 (7.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/28 (14.3%)	4
Dyspnoea	5/28 (17.9%)	5
Skin and subcutaneous tissue disorders
Alopecia	3/28 (10.7%)	3
Night sweats	2/28 (7.1%)	3
Pruritus	3/28 (10.7%)	3
Vascular disorders
Hypotension	2/28 (7.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.