Lymphoma, Non-Hodgkin's
Conditions
Keywords
Celgene, Revlimid, CC-5013, Non-hodgkin's lymphoma, Lenalidomide, CC5013, NHL
Brief summary
Subjects who qualify will receive oral lenalidomide daily on days 1-21 of every 28 day cycle. Treatment will continue until disease progression, or unacceptable adverse events develop
Interventions
DRUGlenalidomide
once daily oral capsule
Sponsors
Celgene
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
Key Inclusion criteria * Biopsy proven aggressive non-hodgkin's lymphoma * Follicular center lymphoma Grade 3. * Diffuse large B-cell lymphoma. * Mantle cell lymphoma. * Transformed lymphoma. * Relapsed or refractory to previous therapy for lymphoma * At least one prior combination chemotherapy regime * Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter * Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2 * Willing to follow the pregnancy precautions Key
Exclusion criteria
* Any of the following laboratory abnormalities. * Absolute neutrophil count (ANC) \< 1,500 cells/mm\^3 (1.5\*10\^9/L). * Platelet count \< 60,000/mm\^3 (60\*10\^9/L). * Calculated creatinine clearance of \<50mL/min * Serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) or Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT) 5.0 times upper limit of normal (ULN). * Serum total bilirubin \> 2.0 mg/dL (34 µmol/L)/conjugated bilirubin \>0.8mg/dL. * Subjects who are candidates for and willing to undergo an autologous stem cell transplant. * History of active Central Nervous System (CNS) lymphoma within the previous 6 months * History of other malignancies within the past year * Positive Human immunodeficiency virus (HIV) or active Hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Categorized by Best Response as Determined by Central Review | Up to 1459 days | Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definitions, refer to Cheson article. * Complete Response(CR): Complete disappearance of all detectable disease and disease-related symptoms if present before therapy; normalization of lab abnormalities assignable to NHL. If bone marrow involved before treatment, must be cleared on repeat biopsy. * Complete Response Unconfirmed(CRu): CR, with one of the following: 1)residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters(SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2)indeterminate bone marrow. * Partial Response(PR): \>50% decrease in 6 largest nodes or nodal masses. Nodes selected according to Cheson. * Stable Disease(SD): Less than PR, but not progressive disease. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response as Determined by Central Review | Up to 1459 days | Kaplan-Meier estimates for the duration of response were calculated for responders and defined as the time from at least a partial response (PR) to progression of disease (PD) or death due to Non-Hodgkin's lymphoma. For response assessment criteria (per Cheson, 1999) see the primary outcome measure in this results posting. |
| Time to Progression as Determined by Central Review | Up to 1459 days | Kaplan-Meier estimate of time-to-progression is calculated as time from the start of study drug therapy to the first observation of disease progression. Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD. |
| Progression-free Survival as Determined by Central Review | Up to 1459 days | Kaplan-Meier estimate of progression-free survival is defined as start of study drug therapy to the first observation of progressive disease or death due to any cause, whichever comes first. Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD. |
| Proportion of Participants Who Experienced Stable Disease or Better as Determined by Central Review | Up to 1459 days | Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definitions, refer to Cheson article. * Complete Response(CR): Complete disappearance of all detectable disease and disease-related symptoms if present before therapy; normalization of lab abnormalities assignable to NHL. If bone marrow involved before treatment, must be cleared on repeat biopsy. * Complete Response Unconfirmed(CRu): CR, with one of the following: 1)residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters(SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2)indeterminate bone marrow. * Partial Response(PR): \>50% decrease in 6 largest nodes or nodal masses. Nodes selected according to Cheson. * Stable Disease(SD): Less than PR, but not progressive disease. |
Countries
Canada, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
217 participants were enrolled and received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide 25 mg oral lenalidomide once daily on Days 1-21 every 28 days | 217 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 44 |
| Overall Study | Death | 9 |
| Overall Study | Lack of Efficacy | 129 |
| Overall Study | Missing | 2 |
| Overall Study | Other | 26 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Lenalidomide |
|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 11.54 |
| Age, Customized < 65 years | 90 Participants |
| Age, Customized > = 65 years | 127 Participants |
| Gender Female | 77 Participants |
| Gender Male | 140 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Diffuse Large Cell Lymphoma | 108 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Follicular Lymphoma, Grade 3 | 19 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Mantle Cell Lymphoma | 57 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Transformed Lymphoma | 33 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participant |
| Race/Ethnicity, Customized Asian/Pacific Islander | 0 Participant |
| Race/Ethnicity, Customized Black | 4 Participant |
| Race/Ethnicity, Customized Hispanic | 2 Participant |
| Race/Ethnicity, Customized Unspecified | 9 Participant |
| Race/Ethnicity, Customized White | 202 Participant |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 188 / 217 |
| serious Total, serious adverse events | 102 / 217 |
Outcome results
Primary
Participants Categorized by Best Response as Determined by Central Review
Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definitions, refer to Cheson article. * Complete Response(CR): Complete disappearance of all detectable disease and disease-related symptoms if present before therapy; normalization of lab abnormalities assignable to NHL. If bone marrow involved before treatment, must be cleared on repeat biopsy. * Complete Response Unconfirmed(CRu): CR, with one of the following: 1)residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters(SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2)indeterminate bone marrow. * Partial Response(PR): \>50% decrease in 6 largest nodes or nodal masses. Nodes selected according to Cheson. * Stable Disease(SD): Less than PR, but not progressive disease. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD.
Time frame: Up to 1459 days
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide | Participants Categorized by Best Response as Determined by Central Review | Stable Disease (SD) | 71 Participants |
| Lenalidomide | Participants Categorized by Best Response as Determined by Central Review | Progressive Disease | 78 Participants |
| Lenalidomide | Participants Categorized by Best Response as Determined by Central Review | Complete Response (CR) | 7 Participants |
| Lenalidomide | Participants Categorized by Best Response as Determined by Central Review | Complete Response Unconfirmed (CRu) | 21 Participants |
| Lenalidomide | Participants Categorized by Best Response as Determined by Central Review | Partial Response (PR) | 40 Participants |
Secondary
Duration of Response as Determined by Central Review
Kaplan-Meier estimates for the duration of response were calculated for responders and defined as the time from at least a partial response (PR) to progression of disease (PD) or death due to Non-Hodgkin's lymphoma. For response assessment criteria (per Cheson, 1999) see the primary outcome measure in this results posting.
Time frame: Up to 1459 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Duration of Response as Determined by Central Review | 18.4 Months |
Secondary
Progression-free Survival as Determined by Central Review
Kaplan-Meier estimate of progression-free survival is defined as start of study drug therapy to the first observation of progressive disease or death due to any cause, whichever comes first. Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD.
Time frame: Up to 1459 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Progression-free Survival as Determined by Central Review | 4.5 Months |
Secondary
Proportion of Participants Who Experienced Stable Disease or Better as Determined by Central Review
Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definitions, refer to Cheson article. * Complete Response(CR): Complete disappearance of all detectable disease and disease-related symptoms if present before therapy; normalization of lab abnormalities assignable to NHL. If bone marrow involved before treatment, must be cleared on repeat biopsy. * Complete Response Unconfirmed(CRu): CR, with one of the following: 1)residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters(SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2)indeterminate bone marrow. * Partial Response(PR): \>50% decrease in 6 largest nodes or nodal masses. Nodes selected according to Cheson. * Stable Disease(SD): Less than PR, but not progressive disease.
Time frame: Up to 1459 days
Population: Tumor Control Rate or Proportion of Participants Who Experienced Stable Disease or Better (SD+PR+CRu+CR) was not analyzed. Overall Response Rate (PR+CRu+CR) is presented as the primary endpoint, and because it is a more widely accepted/used efficacy endpoint than tumor control rate, a decision was made not to analyze tumor control rate.
Secondary
Time to Progression as Determined by Central Review
Kaplan-Meier estimate of time-to-progression is calculated as time from the start of study drug therapy to the first observation of disease progression. Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article. * Progressive Disease(PD): Appearance of new lesion during/end of therapy; \>=50% increase from lowest measurement in SPD.
Time frame: Up to 1459 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Time to Progression as Determined by Central Review | 4.5 Months |