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

Tracking Information

• First Submitted Date: November 29, 2012
• First Posted Date: December 3, 2012
• Results First Submitted Date: October 27, 2017
• Results First Posted Date: February 15, 2019
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: March 20, 2013
• Actual Primary Completion Date: September 28, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2018)

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) [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: November 29, 2012): Proportion of Participants who Achieve Best Overall Disease Response of Complete Response (CR), Complete Response unconfirmed (CRu), Partial Response (PR) or Stable Disease (SD) [ Time Frame: Baseline until Disease Progression or Start of New Anticancer Therapy (Estimated up to 28 Months) ]

Current Secondary Outcome Measures (submitted: October 2, 2018)

• Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR [ Time Frame: 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.
• Duration of Objective Response (DOR) [ Time Frame: 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.
• Progression-Free Survival (PFS) [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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.
• Event-Free Survival [ Time Frame: 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).
• Time to Disease Progression [ Time Frame: 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.
• Disease-Free Survival [ 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) ]
  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.
• Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores [ Time Frame: 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.
• Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib [ Time Frame: Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose ]
• 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 ]
• 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 ]
• PK: Volume of Distribution (Vd) of Abemaciclib [ Time Frame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose ]
• PK: Clearance (CL) of Abemaciclib [ Time Frame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose ]

Original Secondary Outcome Measures (submitted: November 29, 2012)

• Proportion of Participants who Achieve Best Overall Disease Response of CR, CRu or PR [ Time Frame: Baseline until Disease Progression (Estimated up to 28 Months) ]
• Duration of Response [ Time Frame: Date of CR, CRu or PR until Disease Progression or Death Due to Any Cause (Estimated up to 28 Months) ]
• Progression-Free Survival [ Time Frame: Date of First Dose until Diease Progression or Death Due to Any Cause (Estimated up to 28 Months) ]
• Overall Survival [ Time Frame: Date of First Dose until Death Due to Any Cause (Estimated up to 28 Months) ]
• Change from Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score and Subscales [ Time Frame: Baseline, 30 Day Post Therapy (Estimated up to 28 Months) ]
• Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219 and its metabolites [ Time Frame: Predose up to 10 Hours Postdose ]
• PK - Area Under the Concentration-Time Curve (AUC) of LY283219 and its metabolites [ Time Frame: Predose up to 10 Hours Postdose ]
• PK - Terminal Half Life (T 1/2) of LY2835219 and its metabolites [ Time Frame: Predose up to 10 hours Postdose ]
• PK: Volume of Distribution (Vd) of LY2835219 and its metabolites [ Time Frame: Predose up to 10 Hours Postdose ]
• PK: Clearance (CL) of LY2835219 and its metabolites [ Time Frame: Predose up to 10 Hours Postdose ]
• Event-Free Survival [ Time Frame: Baseline until Disease Progression or Death Due to Any Cause (Estimated up to 28 Months) ]
• Time to Disease Progression [ Time Frame: Baseline until Disease Progression (Estimated up to 28 Months) ]
• Disease-Free Survival [ Time Frame: Baseline until Disease Progression (Estimated up to 28 Months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of LY2835219 for Mantle Cell Lymphoma
• Official Title: Phase 2 Study of a CDK4/6 Inhibitor for Patients With Relapsed or Refractory Mantle Cell Lymphoma
• Brief Summary: The purpose of this study is to estimate the disease control rate with abemaciclib for relapsed or refractory mantle cell lymphoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mantle Cell Lymphoma

Intervention

Drug: Abemaciclib

Administered orally

Other Name: LY2835219

Study Arms

Experimental: Abemaciclib

200 milligram (mg) abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle

Intervention: Drug: Abemaciclib

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 2, 2018): 28
• Original Estimated Enrollment (submitted: November 29, 2012): 20
• Actual Study Completion Date: September 5, 2022
• Actual Primary Completion Date: September 28, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany

Administrative Information

• NCT Number: NCT01739309
• Other Study ID Numbers: 13269; I3Y-MC-JPBB ( Other Identifier: Eli Lilly and Company ); 2012-003614-14 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: January 2023