Non-Hodgkins Lymphoma
Conditions
Keywords
NHL, CC5013, Non-Hodgkins Lymphoma, revlimid, cc-5013, celgene
Brief summary
Subjects who qualify will receive lenalidomide daily on days 1-21 of every 28-day cycle. Treatment will continue for up to 52 weeks or until disease progression; subjects who achieve a Complete Response (CR) will receive an additional 2 cycles of treatment prior to discontinuation. Subjects will be followed for progression free survival following discontinuation from the treatment phase
Interventions
DRUGLenalidomide
Sponsors
Prologue Research International
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
1. Understand and voluntarily sign an informed consent form. 2. Age greater than or equal to 18 years at the time of signing the informed consent form 3. Able to adhere to the study visit schedule and other protocol requirements 4. Biopsy-proven non-Hodgkin's lymphoma 5. Indolent lymphoma the following histologies are acceptable: a. Follicular center lymphoma, grades 1, 2; b. Extranodal marginal zone B-cell lymphoma of Mucosa associated lymphoid tissue (MALT) type, c. Nodal marginal zone B-cell lymphoma d. Splenic marginal zone B-cell lymphoma, e. Small lymphocytic lymphoma (SLL), f. Lymphoplasmacytoid lymphoma 6. Relapsed or refractory to previous therapy for lymphoma. Participants must have received at least one prior treatment regimen such as radiation, immunotherapy, chemotherapy, or radioimmunotherapy, and be ineligible or unwilling to undergo an autologous stem cell transplant. There is no limit on the number of prior therapies 7. Participants must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2. 9. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.
Exclusion criteria
1. Any of the following laboratory abnormalities 1. Absolute neutrophil count (ANC) \<1,500 cells/mm\^3 (1.5 x 10\^9/L) 2. Platelet count \<100,000/mm\^3 (100 x 10\^9/L) 3. Serum creatinine \>2.5 mg/dL (221 mmol/L) 4. Serum Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) \>5.0 x upper limit of normal (ULN) 5. Serum total bilirubin \>2.0 mg/dL (34 mmol/L) 2. Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 3. All participants with Central Nervous System (CNS) disease with the exception of those subjects whose CNS disease has been treated with chemotherapy, radiotherapy or surgery and remains asymptomatic, with no active CNS disease, as shown by lumbar puncture, computerized tomography (CT) scan or Magnetic resonance imaging (MRI), for at least 6 months. 4. Prior history of malignancies other than non-Hodgkin's lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the participant has been free of the disease for \> or equal to 1 year. 5. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from signing the informed consent form. 6. Known positive for human immunodeficiency virus (HIV). 7. Pregnant or lactating females. 8. Prior \> or equal to grade 3 allergic reaction/hypersensitivity to thalidomide. 9. Prior \> or equal to grade 3 rash or any desquamating (blistering) rash while taking thalidomide. 10. Prior use of lenalidomide. 11. Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy. 12. Known active Hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response | From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months | Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: • A residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) • Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tumor Control | From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months | Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as • ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. • Appearance of any new lesion during or at the end of therapy. |
| The Duration of Response | From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months | The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate. |
| Progression Free Survival (PFS) | From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months | Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment. |
| Number of Participants With Adverse Events (AEs) | From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months. | The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: • Grade 1 = Mild • Grade 2 = Moderate • Grade 3 = Severe • Grade 4 = Life threatening • Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 4 |
| Overall Study | Lack of Efficacy | 15 |
| Overall Study | Other Observations and options | 14 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Lenalidomide |
|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 10.95 |
| Age, Customized 65 - 75 | 10 participants |
| Age, Customized <65 years | 24 participants |
| Age, Customized >75 years | 9 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 = fully active, no restrictions; | 27 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 = restricted but ambulatory and capable of light | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 2 = ambulatory and capable of self care but unable | 4 participants |
| International Prognostic Index (IPI)] High (4 to 5) | 8 participants |
| International Prognostic Index (IPI)] High/Intermediate (3) | 6 participants |
| International Prognostic Index (IPI)] Low (0 to 1) | 14 participants |
| International Prognostic Index (IPI)] Low/Intermediate (2) | 15 participants |
| NHL Duration | 5.6 years STANDARD_DEVIATION 4.38 |
| Non-Hodgkin's Lymphoma (NHL) Histology Extranodal marginal-zone B-cell type (MALT) | 1 participants |
| Non-Hodgkin's Lymphoma (NHL) Histology Follicular lymphoma grade 1 or 2 | 22 participants |
| Non-Hodgkin's Lymphoma (NHL) Histology Nodal marginal-zone B-cell lymphoma | 2 participants |
| Non-Hodgkin's Lymphoma (NHL) Histology Small Lymphocytic lymphoma | 18 participants |
| Non-Hodgkin's Lymphoma (NHL)-Stage Stage I | 1 participants |
| Non-Hodgkin's Lymphoma (NHL)-Stage Stage II | 11 participants |
| Non-Hodgkin's Lymphoma (NHL)-Stage Stage III | 6 participants |
| Non-Hodgkin's Lymphoma (NHL)-Stage Stage IV | 25 participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 participants |
| Race/Ethnicity, Customized Black | 4 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants |
| Race/Ethnicity, Customized Other = Unspecified | 1 participants |
| Race/Ethnicity, Customized White | 37 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 43 |
| serious Total, serious adverse events | 18 / 43 |
Outcome results
Primary
Percentage of Participants With Response
Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: • A residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) • Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
Time frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
Population: Intent-to-treat (ITT) population, which included all enrolled patients who received at least 1 dose of study drug. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide | Percentage of Participants With Response | 23.3 percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs)
The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: • Grade 1 = Mild • Grade 2 = Moderate • Grade 3 = Severe • Grade 4 = Life threatening • Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Time frame: From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months.
Population: Safety Population, which includes all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide | Number of Participants With Adverse Events (AEs) | At least one Adverse Event (AE) | 42 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | ≥ 1 AE related to study drug | 37 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | Grade (GR) 3-5 AE | 27 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | Grade 3-5 AE related to study drug | 24 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | Serious adverse event (SAE) | 18 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | SAE related to study drug | 10 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of study drug | 9 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | Related AE leading to study drug discontinuation | 5 participants |
| Lenalidomide | Number of Participants With Adverse Events (AEs) | AE leading to dose reduction or interruption | 27 participants |
Secondary
Percentage of Participants With Tumor Control
Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as • ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. • Appearance of any new lesion during or at the end of therapy.
Time frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
Population: Intent-to-treat (ITT) population. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide | Percentage of Participants With Tumor Control | 60.5 percentage of participants |
Secondary
Progression Free Survival (PFS)
Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.
Time frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
Population: Intent to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | Progression Free Survival (PFS) | 4.4 months |
Secondary
The Duration of Response
The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.
Time frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
Population: Includes participants with a response to treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide | The Duration of Response | NA months |