Clinical trial NCT01739309: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Non- Hodgkins Lymphoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-12-03
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: 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)
timeFrame: From Date of First Dose until Disease Progression or Death or Start of New Anticancer Therapy (Up to 28 Months)
Secondary outcomes:
measure: Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR
timeFrame: From Date of First Dose until Disease Progression (Up to 28 Months)
measure: Duration of Objective Response (DOR)
timeFrame: From Date of CR, CRu or PR until Disease Progression or Death Due to Any Cause (Up to 28 Months)
measure: Progression-Free Survival (PFS)
timeFrame: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up to 28 Months)
measure: Overall Survival (OS)
timeFrame: From Date of First Dose until Death Due to Any Cause (Up to 28 Months)
measure: Event-Free Survival
timeFrame: From Date of First Dose until Disease Progression, Discontinuation of Treatment, or Death Due to Any Cause (Up to 28 Months)
measure: Time to Disease Progression
timeFrame: From Date of First Dose Until Disease Progression (Up to 28 Months)
measure: Disease-Free Survival
timeFrame: 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)
measure: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores
timeFrame: Baseline, Cycle 5 (Up To Day 140)
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
timeFrame: Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
measure: PK - Area Under the Concentration-Time Curve From Zero to Last Time Point (AUC[0-tlast]) of Abemaciclib
timeFrame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
measure: PK - Terminal Half Life (T 1/2) of Abemaciclib
timeFrame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
measure: PK: Volume of Distribution (Vd) of Abemaciclib
timeFrame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
measure: PK: Clearance (CL) of Abemaciclib
timeFrame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Other outcomes:
Locations:
city: Lille
country: France
facility: 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.
city: Pessac
country: France
facility: 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.
city: Homburg
country: Germany
facility: 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.
city: Kassel
country: Germany
facility: 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.
city: Mainz
country: Germany
facility: 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.
city: Nürnberg
country: Germany
facility: 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.
city: Ulm
country: Germany
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.