Mantle Cell Lymphoma
Conditions
Keywords
Non- Hodgkins Lymphoma
Brief summary
The purpose of this study is to estimate the disease control rate with abemaciclib for relapsed or refractory mantle cell lymphoma.
Interventions
DRUGAbemaciclib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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% confidence interval (CI) was estimated for treated participants using the Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | 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 | Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose | — |
| PK - Terminal Half Life (T 1/2) of Abemaciclib | Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose | — |
| PK: Volume of Distribution (Vd) of Abemaciclib | Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose | — |
| PK: Clearance (CL) of Abemaciclib | Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose | — |
| 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. |
Countries
France, Germany
Participant flow
Pre-assignment details
Completers are those who died, or are alive and being followed at the end of the trial but off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Abemaciclib |
|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment France | 13 Participants |
| Region of Enrollment Germany | 15 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 13 / 28 |
Outcome results
Primary
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)
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% confidence interval (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)
Population: All participants who received at least one dose of study drug and had evaluable DCR data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib | 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) | 71.4 percentage of participants |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores
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)
Population: All participants who received at least one dose of study drug and had baseline and post baseline FACT-Lym data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib | Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores | Physical Well-Being (PWB) Subscale Score | 0.2 units on a scale | Standard Deviation 5.6 |
| Abemaciclib | Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores | Functional (FWB) Subscale Score | -0.9 units on a scale | Standard Deviation 4.5 |
| Abemaciclib | Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores | LYM Subscale Score | 1.1 units on a scale | Standard Deviation 5.2 |
| Abemaciclib | Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores | FACT-Lym TOI Score | 0.5 units on a scale | Standard Deviation 12.5 |
Secondary
Disease-Free Survival
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)
Population: All participants who received at least one dose of study drug. 5 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Disease-Free Survival | 9.20 Months |
Secondary
Duration of Objective Response (DOR)
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)
Population: All participants who received at least one dose of study drug and achieved BOR. 4 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Duration of Objective Response (DOR) | 12.39 months |
Secondary
Event-Free Survival
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)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Event-Free Survival | 11.29 Months |
Secondary
Overall Survival (OS)
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)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Overall Survival (OS) | 16.03 Months |
Secondary
Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR
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)
Population: All participants who received at least one dose of study drug and had evaluable BOR data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib | Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR | 35.7 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
Time frame: Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib | 189 nanogram/milliliter (ng/ml) | Geometric Coefficient of Variation 59 |
Secondary
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
Population: All randomized who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib | PK - Area Under the Concentration-Time Curve From Zero to Last Time Point (AUC[0-tlast]) of Abemaciclib | 978 hour*nanogram/milliliter (hr*ng/ml) | Geometric Coefficient of Variation 61 |
Secondary
PK: Clearance (CL) of Abemaciclib
Time frame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Population: Zero participants were analyzed. CL was not calculated due to PK sampling schedule was not suitable for estimation of these PK parameters.
Secondary
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
Population: 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.
Secondary
PK: Volume of Distribution (Vd) of Abemaciclib
Time frame: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose
Population: Zero participants were analyzed. Vd was not calculated by non-compartmental analysis with the available data.
Secondary
Progression-Free Survival (PFS)
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)
Population: All participants who received at least one dose of study drug. 9 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Progression-Free Survival (PFS) | 8.18 Months |
Secondary
Time to Disease Progression
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)
Population: All participants who received at least one dose of study drug. 17 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Time to Disease Progression | 12.85 Months |