Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)
Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01197560
Collaborator
(none)
111
57
2
91.1
1.9
0
Study Details
Study Description
Brief Summary
The purpose of this study is to compare lenalidomide to a control drug and see which one delays Diffuse Large B-Cell Lymphoma (DLBCL) disease progression longer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Detailed Description
This research study is for patients who have been diagnosed with Diffuse Large B-cell Lymphoma (DLBCL) that did not respond to (refractory) or that has come back after chemotherapy treatment (relapsed). Lymphoma is a cancer of a type of blood cell called lymphocytes. DLBCL is just one type of lymphoma. Within DLBCL there are two different subtypes called Germinal Center B-cell (GCB) and non-GCB which can be determined by cell surface marker tests or by gene expression tests. Scientists can look at cells and genes in the laboratory and see that the two kinds are different, but they don't know yet what the difference means. To patients and doctors these two kinds seem the same. Right now doctors don't usually do tests to find out which kind a patient has because the treatment is the same for both.
This study will have two stages, 1 and 2. The main purpose of Stage 1 is to separate patients by subtype and then test whether patients taking lenalidomide or any one of four other drugs have a better response. It is possible that lenalidomide will work better than one of the other drugs in zero, one, or both subtypes. Stage 2 will further test only the subtype(s) from Stage 1 that showed a good response to lenalidomide. The main purpose of Stage 2 is to test how long patients are disease free on lenalidomide compared to one of the four other drugs.
On 29 January 2013 the enrolment goal for the Stage 1 portion of the study was met and enrollment was stopped. The final analysis for Stage 1 was performed as of the 04 Jul 2013 data cutoff date. According to the Stage 1 results as assessed by the independent response adjudication committee (IRAC), neither subtype met the pre specified requirement to be further studied in Stage 2. Additionally, a suitable assay for the selection of participants for the Stage 2 study was not available. Therefore, on 6 January 2014, Celgene decided to not open Stage 2.
Study Design
Study Type:
Interventional
Actual Enrollment
:
111 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2/3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Lenalidomide (Revlimid ®) Versus Investigator's Choice in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Actual Study Start Date
:
Sep 2, 2010
Actual Primary Completion Date
:
Jul 4, 2013
Actual Study Completion Date
:
Apr 5, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lenalidomide Lenalidomide 25 mg capsules by mouth on days 1-21 of each 28 day cycle. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg). |
Drug: Lenalidomide
Lenalidomide 25 mg orally for 21/28 days until Diffuse Large B-Cell Lymphoma (DLBCL) progressive disease. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).
|
| Active Comparator: Investigators Choice One of the following: Gemcitabine, Oxaliplatin, Rituximab, or Etoposide |
Drug: Gemcitabine
Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m^2 intravenous (IV) administration on days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 every 28 days for 6 Cycles
Drug: Oxaliplatin
Suggested starting dose and regimen for Oxaliplatin is 100 mg/m^2 IV day 1 for 21 days for 6 Cycles
Drug: Rituximab
Suggested starting dose for Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only)
Drug: Etoposide
Suggested starting doses for Etoposide are:
100 mg/m^2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m^2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-10 every 28 days for 6 Cycles
|
Outcome Measures
Primary Outcome Measures
- Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC) [From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.]
An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease.
- Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease.
Secondary Outcome Measures
- Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment [From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event.The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death
- Stage 2: Overall Response Rate (ORR) [Approximately 3.5 years]
ORR is defined as: Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
- Stage 2: Duration of Response (DoR) [Approximately 3.5 years]
Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
- Stage 2: Overall Survival (OS) [Approximately 3.5 years]
Overall survival was defined as time from randomization until death of any cause.
- Stage 2: Duration of Complete Response [Approximately 3.5 years]
Length of time of complete response (Complete Response + Complete Response unconfirmed) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
- Stage 2: Overall Response Rate for With a Duration of Response Lasting ≥ 16 Weeks [Approximately 3.5 years]
Complete Response + Complete Response unconfirmed + Partial Response for participants with a duration of response lasting ≥ 16 weeks based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
- Stage 2: Time to Progression [Approximately 3.5 years]
Length of time until disease progression occurs
- Stage 2: Health Related Quality of Life Questionnaires [Approximately 3.5 years]
Quality of Life based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D assessments
Other Outcome Measures
- Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response.
- Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
A complete response was defined as participants with a complete response (CR), or unconfirmed complete response (CRu) based on IWG 1999 Response Criteria for NHL as assessed by the investigator. A CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRu) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.
- Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Duration of overall response was calculated as the time of initial response (CR+CRu+PR) until documented disease progression determinted by computerized scan CT scan or MRI or death due to lymphoma, whichever occurred earlier, for participants who responded.
- Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Duration of complete response was defined as the time from the first documented complete response (CR + CRu) until the first disease progression or death for participants who had a CR.
- Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause.
- Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase [From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.]
Overall survival was defined as time from randomization until death of any cause.
- Stage 2: Progression-Free Survival [Approximately 3.5 years]
Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG].
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL).
-
Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline, and one additional combination chemotherapy or stem cell transplant.
-
Measurable DLBCL disease by computed tomograph (CT) / magnetic resonance imagining (MRI).
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
Exclusion Criteria:
-
Diagnosis of lymphoma histologies other than DLBCL.
-
History of malignancies, other than DLBCL, unless the patient has been disease free for 3 years or more.
-
Eligible for autologous stem cell transplant.
-
Known seropositive for, or history of, active human immunodeficiency virus (HIV) hepatitis B virus (HBV), hepatitis C virus (HCV)
-
Neuropathy grade 4.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Providence St Joseph Medical Center/Cancer Center | Burbank | California | United States | 91505 |
| 2 | MD Anderson Cancer Center Orlando | Orlando | Florida | United States | 32806 |
| 3 | Emory University | Atlanta | Georgia | United States | 30322 |
| 4 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 5 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 6 | Center for Cancer and Blood Disorders | Bethesda | Maryland | United States | 20817 |
| 7 | University of Michigan, Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48105 |
| 8 | Hattiesburg Clinic | Hattiesburg | Mississippi | United States | 39402 |
| 9 | Washington University Siteman Cancer Center | Saint Louis | Missouri | United States | 63110 |
| 10 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 11 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 12 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 13 | MD Anderson Houston | Houston | Texas | United States | 77030 |
| 14 | Royal Adelaide Hospital | Adelaide | Australia | 5000 | |
| 15 | Royal Brisbaine and Womens Hospital | Herston | Australia | 4029 | |
| 16 | Princess Alexandra Hospital | Woolloongabba | Australia | 4102 | |
| 17 | Innsbruck University Hospital | Innsbruck | Austria | A6020 | |
| 18 | Universitätsklinikum Salzburg | Salzburg | Austria | A-5020 | |
| 19 | Medical University of Vienna | Vienna | Austria | A-1090 | |
| 20 | University Hospital Hradec Kralove | Hradec Kralove 5 | Czechia | 5005 | |
| 21 | Charles University | Praha | Czechia | 12808 | |
| 22 | ICH CHU Brest- C.H.U. MORAVAN | Brest Cedex 2 | France | 29609 | |
| 23 | CHU de Grenoble-Hopital Albert Michallon | Grenoble | France | 38043 | |
| 24 | Chd -Vendee | La Roche Sur Yon | France | 85205 | |
| 25 | Centre Hospitalier Lyon Sud | Lyon | France | 69495 | |
| 26 | Institute Paoli-Calmette | Marsielle | France | 13009 | |
| 27 | Hotel Dieu | Nantes Cedex 1 | France | 44903 | |
| 28 | Hôpital Saint Jean | Perpignan | France | 66046 | |
| 29 | CHRU-Hopital du Haut -Leveque | Pessac | France | 33604 | |
| 30 | CHU de Rennes Hopital de Pontchaillou | Rennes | France | 35033 | |
| 31 | University Hospital OF Toulouse Purpan | Toulouse | France | 31059 | |
| 32 | Hopital de Brabois Adultes | Vandoeuvre-les Nancy cedex | France | 54511 | |
| 33 | Istituto di Ematologica Istituto di Ematologica " L.e. A. Seragnoli' Azienda Ospedaliera Universitaria Policlinico | Bologna | Italy | 40138 | |
| 34 | Azienda Ospedaliera Universitaria Careggi | Firenze | Italy | 50141 | |
| 35 | Clinica Ematologica, A.O.U. San Martino di Genova | Genova | Italy | 16132 | |
| 36 | IEO istituto Europeo di Oncologia | Miano | Italy | 201401 | |
| 37 | Universita Federico II di Napoli Nuovo Policlinico | Napoli | Italy | 80131 | |
| 38 | Fondazione IRCCS Policlinico San Matteo | Pavia | Italy | 27100 | |
| 39 | Irccs/Crob | Rionero In Vulture (PZ) | Italy | 85208 | |
| 40 | Policlinico Tor Vergata (Universta Tor Vergata) | Roma | Italy | 00133 | |
| 41 | Azienda Ospedaliera di Perugai Ospedale S. Maria della Miseri | Terni | Italy | 6156 | |
| 42 | Hospital Universitari Vll D' Hebron | Barcelona | Spain | 8035 | |
| 43 | Hospital Universitario Reina Sofia | Cordoba | Spain | 14004 | |
| 44 | Hospital Costa Del Sol | Marbella | Spain | 29600 | |
| 45 | CH de Orense | Ourense | Spain | 32005 | |
| 46 | Complejo Hospitalario de Navarra | Pamplona | Spain | 31008 | |
| 47 | Hosptial Clinico Universitario de Salamanca | Salamanca | Spain | 37007 | |
| 48 | Onkologiska kliniken | Umea | Sweden | 90185 | |
| 49 | Akademiska Sjukhuset | Uppsala | Sweden | 75185 | |
| 50 | Royal Bournemouth Hospital Haematology | Bournemouth | United Kingdom | BH7 7DW | |
| 51 | Royal Devon and Exeter Hospital Haematology Department | Exeter | United Kingdom | EX2 5DW | |
| 52 | St. James Institute of Oncology | Leeds | United Kingdom | LS9 7TF | |
| 53 | Royal Mardsen Hospital - Fulham (Satellite Site) | London | United Kingdom | SW3 6U | |
| 54 | The Christie Foundation Trust, I'st Floor, Haemotology Oncology Outpatients, Lymphoma Team | Manchester | United Kingdom | M20 4BX | |
| 55 | Derrford Hospital | Plymouth | United Kingdom | PL6 8DH | |
| 56 | Southhampton University Hospital NHS Trust | Southhampton | United Kingdom | SO16 6YD | |
| 57 | Royal Mardsen NHS Foundation Trust | Sutton | United Kingdom | SM2 SPT |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Adrian Kilcoyne, MD, Celgene Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01197560
Other Study ID Numbers:
- CC-5013-DLC-001
First Posted:
Sep 9, 2010
Last Update Posted:
Nov 25, 2019
Last Verified:
Nov 1, 2019
Keywords provided by Celgene
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Screening and enrollment occurred at 43 sites, including 10 in the United States, 9 in France, 7 in the United Kingdom; 4 in Spain, 4 in Italy, 3 each in Austria and Australia, 2 in the Czech Republic, and 1 in Sweden. |
|---|---|
| Pre-assignment Detail | Participants were stratified into Germinal center B-cell (GCB) or non-GCB subtypes and randomized 1:1 to receive lenalidomide or investigator's choice treatment (one of the single-agent reference therapies [gemcitabine, rituximab, etoposide, or oxaliplatin) |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Period Title: Overall Study | ||
| STARTED | 54 | 57 |
| Received ≥ One Dose Study Drug | 54 | 55 |
| Lenalidomide Crossover | 0 | 29 |
| Discontinued Treatment After ≥ 6 Cycles | 14 | 0 |
| COMPLETED | 0 | 4 |
| NOT COMPLETED | 54 | 53 |
Baseline Characteristics
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles | Total of all reporting groups |
| Overall Participants | 51 | 51 | 102 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.7
(13.43)
|
62.8
(13.94)
|
63.75
(13.69)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
21
41.2%
|
20
39.2%
|
41
40.2%
|
| Male |
30
58.8%
|
31
60.8%
|
61
59.8%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
1
2%
|
1
2%
|
2
2%
|
| Black/African American |
0
0%
|
1
2%
|
1
1%
|
| White |
38
74.5%
|
36
70.6%
|
74
72.5%
|
| Missing |
9
17.6%
|
11
21.6%
|
20
19.6%
|
| Other (Unspecified) |
3
5.9%
|
2
3.9%
|
5
4.9%
|
| Eastern Cooperative Oncology Performance Status (ECOG)] (Count of Participants) | |||
| 0 = (Fully Active) |
18
35.3%
|
15
29.4%
|
33
32.4%
|
| 1 (Restrictive but Ambulatory) |
24
47.1%
|
28
54.9%
|
52
51%
|
| 2 (Ambulatory but Unable to Work) |
7
13.7%
|
8
15.7%
|
15
14.7%
|
| 3 (Limited Self-Care) |
0
0%
|
0
0%
|
0
0%
|
| 4 (Completely Disabled) |
1
2%
|
0
0%
|
1
1%
|
| Missing |
1
2%
|
0
0%
|
1
1%
|
| Creatinine Clearance (CrCl) (Count of Participants) | |||
| ≥ 60 mL/min |
32
62.7%
|
43
84.3%
|
75
73.5%
|
| ≥ 30 but < 60 mL/min |
18
35.3%
|
7
13.7%
|
25
24.5%
|
| Missing |
1
2%
|
1
2%
|
2
2%
|
| Disease Stage of DLBCL at Enrollment (Count of Participants) | |||
| IA |
1
2%
|
3
5.9%
|
4
3.9%
|
| IB |
1
2%
|
0
0%
|
1
1%
|
| IIA |
8
15.7%
|
7
13.7%
|
15
14.7%
|
| IIB |
3
5.9%
|
1
2%
|
4
3.9%
|
| IIIA |
13
25.5%
|
13
25.5%
|
26
25.5%
|
| IIIB |
2
3.9%
|
4
7.8%
|
6
5.9%
|
| IVA |
17
33.3%
|
14
27.5%
|
31
30.4%
|
| IVB |
6
11.8%
|
9
17.6%
|
15
14.7%
|
| Diffuse Large B-Cell Lymphoma (DLBCL) Subtypes - Germinal Center B-Cell (GCB) and non-GCB (Count of Participants) | |||
| Germinal Center B-Cell Type |
23
45.1%
|
25
49%
|
48
47.1%
|
| Non-Germinal Center B-Cell Type |
28
54.9%
|
26
51%
|
54
52.9%
|
Outcome Measures
| Title | Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC) |
|---|---|
| Description | An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease. |
| Time Frame | From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent to Treat (mITT) population was defined as all participants randomized who had a diffuse large B-cell lymphoma (DLBCL) diagnosis and either germinal center B-cell subtype (GCB) or non-GCB subtype confirmed by central pathology, and who received at least one dose of study drug (lenalidomide or investigator's choice). |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 51 | 51 |
| ORR for All Participants |
27.5
53.9%
|
11.8
23.1%
|
| GCB Subtype |
26.1
51.2%
|
12.0
23.5%
|
| Non-GCB |
28.6
56.1%
|
11.5
22.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | Pertains to all participants; row 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.079 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Investigators Choice (IC) |
|---|---|---|
| Comments | Pertains to GCB Subtype; row 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.279 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Investigators Choice (IC) |
|---|---|---|
| Comments | Pertains to non-GCB Sub-type; row 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.179 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase |
|---|---|
| Description | Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 51 | 51 |
| Number (95% Confidence Interval) [Percentage of participants] |
29.4
57.6%
|
13.7
26.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | Pertains to all participants | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
|---|---|
| Description | Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 51 | 51 |
| Median (95% Confidence Interval) [percentage of participants] |
23.5
46.1%
|
9.8
19.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
|---|---|
| Description | A complete response was defined as participants with a complete response (CR), or unconfirmed complete response (CRu) based on IWG 1999 Response Criteria for NHL as assessed by the investigator. A CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRu) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 51 | 51 |
| Number (95% Confidence Interval) [percentage of participants] |
13.7
26.9%
|
3.9
7.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | Pertains to all participants; row 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
|---|---|
| Description | Duration of overall response was calculated as the time of initial response (CR+CRu+PR) until documented disease progression determinted by computerized scan CT scan or MRI or death due to lymphoma, whichever occurred earlier, for participants who responded. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| For DoR, the population included participants who had an overall response. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 15 | 7 |
| Median (95% Confidence Interval) [Weeks] |
64.7
|
63.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.529 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
|---|---|
| Description | Duration of complete response was defined as the time from the first documented complete response (CR + CRu) until the first disease progression or death for participants who had a CR. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| For DoCR, the population included participants who had a CR. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 7 | 2 |
| Median (95% Confidence Interval) [Weeks] |
66.4
|
179.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.972 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase |
|---|---|
| Description | Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 51 | 51 |
| Median (95% Confidence Interval) [Weeks] |
9.6
|
7.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.020 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase |
|---|---|
| Description | Overall survival was defined as time from randomization until death of any cause. |
| Time Frame | From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 51 | 51 |
| Median (95% Confidence Interval) [Weeks] |
31.0
|
24.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide, Investigators Choice (IC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.211 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment |
|---|---|
| Description | A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event.The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death |
| Time Frame | From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all participants who received at least one dose of lenalidomide or IC regimen. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 54 | 55 |
| Any TEAEs |
54
105.9%
|
55
107.8%
|
| Any Treatment Related TEAE |
49
96.1%
|
45
88.2%
|
| Any TEAE Grade ≥ 3 |
43
84.3%
|
53
103.9%
|
| Any TEAE Grade ≥ 4 |
29
56.9%
|
36
70.6%
|
| Any TEAE Grade 5 |
9
17.6%
|
18
35.3%
|
| Any TEAE Grade 3 or 4 |
42
82.4%
|
52
102%
|
| Any Treatment Related TEAE Grade ≥ 3 |
30
58.8%
|
39
76.5%
|
| Any Treatment Related TEAEs Grade ≥ 4 |
15
29.4%
|
21
41.2%
|
| Any Treatment Related TEAE Grade 5 |
0
0%
|
2
3.9%
|
| Any Treatment Related TEAE Grade 3 or 4 |
30
58.8%
|
39
76.5%
|
| Any Serious Adverse Events (SAEs) |
31
60.8%
|
42
82.4%
|
| Any Treated Related SAEs |
14
27.5%
|
21
41.2%
|
| Any AE leading to stopping of study drug |
11
21.6%
|
17
33.3%
|
| Any drug related AE leading to halt of study drug |
5
9.8%
|
4
7.8%
|
| Any AE leading to dose interruption/reduct |
32
62.7%
|
34
66.7%
|
| Any drug related AE leading to interruption/reduct |
27
52.9%
|
30
58.8%
|
| Title | Stage 2: Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as: Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999). |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ORR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Duration of Response (DoR) |
|---|---|
| Description | Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999). |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| DoR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Overall Survival (OS) |
|---|---|
| Description | Overall survival was defined as time from randomization until death of any cause. |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| OS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Progression-Free Survival |
|---|---|
| Description | Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG]. |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| PFS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Duration of Complete Response |
|---|---|
| Description | Length of time of complete response (Complete Response + Complete Response unconfirmed) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999). |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of CR was not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Overall Response Rate for With a Duration of Response Lasting ≥ 16 Weeks |
|---|---|
| Description | Complete Response + Complete Response unconfirmed + Partial Response for participants with a duration of response lasting ≥ 16 weeks based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999). |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall Response Rate for with a Duration of Response Lasting ≥ 16 weeks was not analyzed: the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Time to Progression |
|---|---|
| Description | Length of time until disease progression occurs |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Time to progression was not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (Control Arm) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide. |
| Measure Participants | 0 | 0 |
| Title | Stage 2: Health Related Quality of Life Questionnaires |
|---|---|
| Description | Quality of Life based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D assessments |
| Time Frame | Approximately 3.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Health Related Quality of Life Instruments were not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started. |
| Arm/Group Title | Lenalidomide | Investigators Choice (IC) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | From first dose of study drug to the final data cut-off date of 18 May 2018; the median study duration of 27.0 and 19.7 weeks, respectively. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The AEs were based on the overall treatment phase that includes both core treatment phase and crossover phase. Two participants in the investigator choice arm elected to discontinue before cycle 1; secondary primary malignancies were monitored up to final database lock of 18 May 2018 | |||
| Arm/Group Title | Lenalidomide | Investigator's Choice | ||
| Arm/Group Description | Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. | Investigator's Choice | ||
All Cause Mortality |
||||
| Lenalidomide | Investigator's Choice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/54 (88.9%) | 51/55 (92.7%) | ||
Serious Adverse Events |
||||
| Lenalidomide | Investigator's Choice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/54 (57.4%) | 42/55 (76.4%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 4/54 (7.4%) | 3/55 (5.5%) | ||
| FEBRILE BONE MARROW APLASIA | 0/54 (0%) | 1/55 (1.8%) | ||
| FEBRILE NEUTROPENIA | 4/54 (7.4%) | 2/55 (3.6%) | ||
| LYMPH NODE PAIN | 0/54 (0%) | 1/55 (1.8%) | ||
| THROMBOCYTOPENIA | 1/54 (1.9%) | 3/55 (5.5%) | ||
| Cardiac disorders | ||||
| ATRIAL FIBRILLATION | 1/54 (1.9%) | 0/55 (0%) | ||
| CARDIAC ARREST | 0/54 (0%) | 1/55 (1.8%) | ||
| CARDIAC FAILURE CONGESTIVE | 1/54 (1.9%) | 0/55 (0%) | ||
| CARDIO-RESPIRATORY ARREST | 0/54 (0%) | 1/55 (1.8%) | ||
| MYOCARDIAL INFARCTION | 0/54 (0%) | 1/55 (1.8%) | ||
| SUPRAVENTRICULAR TACHYCARDIA | 1/54 (1.9%) | 0/55 (0%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 0/54 (0%) | 1/55 (1.8%) | ||
| COLITIS ULCERATIVE | 1/54 (1.9%) | 0/55 (0%) | ||
| DIARRHOEA | 0/54 (0%) | 1/55 (1.8%) | ||
| DUODENAL OBSTRUCTION | 1/54 (1.9%) | 0/55 (0%) | ||
| GASTROINTESTINAL HAEMORRHAGE | 1/54 (1.9%) | 0/55 (0%) | ||
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/54 (1.9%) | 0/55 (0%) | ||
| ILEUS | 1/54 (1.9%) | 1/55 (1.8%) | ||
| LARGE INTESTINE PERFORATION | 1/54 (1.9%) | 0/55 (0%) | ||
| LOWER GASTROINTESTINAL HAEMORRHAGE | 1/54 (1.9%) | 0/55 (0%) | ||
| NAUSEA | 0/54 (0%) | 1/55 (1.8%) | ||
| SMALL INTESTINAL OBSTRUCTION | 1/54 (1.9%) | 0/55 (0%) | ||
| VOMITING | 0/54 (0%) | 3/55 (5.5%) | ||
| General disorders | ||||
| ASTHENIA | 0/54 (0%) | 2/55 (3.6%) | ||
| DEATH | 1/54 (1.9%) | 0/55 (0%) | ||
| FATIGUE | 0/54 (0%) | 1/55 (1.8%) | ||
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/54 (1.9%) | 2/55 (3.6%) | ||
| MULTIPLE ORGAN DYSFUNCTION SYNDROME | 0/54 (0%) | 1/55 (1.8%) | ||
| NON-CARDIAC CHEST PAIN | 0/54 (0%) | 1/55 (1.8%) | ||
| PERFORMANCE STATUS DECREASED | 0/54 (0%) | 1/55 (1.8%) | ||
| PYREXIA | 2/54 (3.7%) | 2/55 (3.6%) | ||
| Hepatobiliary disorders | ||||
| BILE DUCT OBSTRUCTION | 1/54 (1.9%) | 0/55 (0%) | ||
| Infections and infestations | ||||
| CELLULITIS | 0/54 (0%) | 4/55 (7.3%) | ||
| DIARRHOEA INFECTIOUS | 0/54 (0%) | 1/55 (1.8%) | ||
| GASTROENTERITIS | 1/54 (1.9%) | 1/55 (1.8%) | ||
| INFECTION | 1/54 (1.9%) | 1/55 (1.8%) | ||
| LOWER RESPIRATORY TRACT INFECTION | 1/54 (1.9%) | 0/55 (0%) | ||
| LUNG ABSCESS | 0/54 (0%) | 1/55 (1.8%) | ||
| LUNG INFECTION | 1/54 (1.9%) | 1/55 (1.8%) | ||
| LYMPH NODE ABSCESS | 0/54 (0%) | 1/55 (1.8%) | ||
| NEUTROPENIC SEPSIS | 0/54 (0%) | 1/55 (1.8%) | ||
| PNEUMONIA | 3/54 (5.6%) | 3/55 (5.5%) | ||
| RESPIRATORY TRACT INFECTION | 1/54 (1.9%) | 0/55 (0%) | ||
| SEPSIS | 1/54 (1.9%) | 2/55 (3.6%) | ||
| SEPTIC SHOCK | 1/54 (1.9%) | 2/55 (3.6%) | ||
| STAPHYLOCOCCAL SEPSIS | 0/54 (0%) | 1/55 (1.8%) | ||
| SUBCUTANEOUS ABSCESS | 0/54 (0%) | 1/55 (1.8%) | ||
| URINARY TRACT INFECTION | 2/54 (3.7%) | 0/55 (0%) | ||
| WOUND INFECTION | 0/54 (0%) | 1/55 (1.8%) | ||
| Injury, poisoning and procedural complications | ||||
| FALL | 0/54 (0%) | 1/55 (1.8%) | ||
| Investigations | ||||
| BLOOD CREATININE INCREASED | 0/54 (0%) | 1/55 (1.8%) | ||
| NEUTROPHIL COUNT DECREASED | 1/54 (1.9%) | 0/55 (0%) | ||
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 1/54 (1.9%) | 1/55 (1.8%) | ||
| HYPERCALCAEMIA | 1/54 (1.9%) | 3/55 (5.5%) | ||
| TUMOUR LYSIS SYNDROME | 1/54 (1.9%) | 1/55 (1.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| BACK PAIN | 1/54 (1.9%) | 0/55 (0%) | ||
| JOINT SWELLING | 1/54 (1.9%) | 0/55 (0%) | ||
| PAIN IN EXTREMITY | 0/54 (0%) | 2/55 (3.6%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| BASAL CELL CARCINOMA | 1/54 (1.9%) | 1/55 (1.8%) | ||
| DIFFUSE LARGE B-CELL LYMPHOMA | 4/54 (7.4%) | 10/55 (18.2%) | ||
| GASTROINTESTINAL TRACT ADENOMA | 0/54 (0%) | 1/55 (1.8%) | ||
| LEUKAEMIA | 1/54 (1.9%) | 0/55 (0%) | ||
| LYMPHOMA | 0/54 (0%) | 1/55 (1.8%) | ||
| NON-HODGKIN'S LYMPHOMA | 0/54 (0%) | 1/55 (1.8%) | ||
| RECTOSIGMOID CANCER METASTATIC | 0/54 (0%) | 1/55 (1.8%) | ||
| TUMOUR FLARE | 1/54 (1.9%) | 0/55 (0%) | ||
| Nervous system disorders | ||||
| CAUDA EQUINA SYNDROME | 0/54 (0%) | 1/55 (1.8%) | ||
| CEREBROVASCULAR ACCIDENT | 1/54 (1.9%) | 0/55 (0%) | ||
| DIZZINESS | 0/54 (0%) | 1/55 (1.8%) | ||
| NERVE ROOT COMPRESSION | 0/54 (0%) | 1/55 (1.8%) | ||
| SEIZURE | 1/54 (1.9%) | 1/55 (1.8%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 0/54 (0%) | 1/55 (1.8%) | ||
| MENTAL STATUS CHANGES | 0/54 (0%) | 1/55 (1.8%) | ||
| Renal and urinary disorders | ||||
| ACUTE KIDNEY INJURY | 0/54 (0%) | 1/55 (1.8%) | ||
| HAEMATURIA | 0/54 (0%) | 2/55 (3.6%) | ||
| HYDRONEPHROSIS | 1/54 (1.9%) | 0/55 (0%) | ||
| NEPHROTIC SYNDROME | 1/54 (1.9%) | 0/55 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| ACUTE PULMONARY OEDEMA | 0/54 (0%) | 1/55 (1.8%) | ||
| DYSPNOEA | 2/54 (3.7%) | 1/55 (1.8%) | ||
| LARYNGEAL OBSTRUCTION | 1/54 (1.9%) | 0/55 (0%) | ||
| OROPHARYNGEAL PAIN | 1/54 (1.9%) | 0/55 (0%) | ||
| PHARYNGEAL INFLAMMATION | 0/54 (0%) | 1/55 (1.8%) | ||
| PLEURAL EFFUSION | 0/54 (0%) | 1/55 (1.8%) | ||
| PULMONARY EMBOLISM | 2/54 (3.7%) | 1/55 (1.8%) | ||
| RESPIRATORY FAILURE | 1/54 (1.9%) | 1/55 (1.8%) | ||
| STRIDOR | 1/54 (1.9%) | 0/55 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| FUNGATING WOUND | 0/54 (0%) | 1/55 (1.8%) | ||
| Vascular disorders | ||||
| DEEP VEIN THROMBOSIS | 0/54 (0%) | 1/55 (1.8%) | ||
| EMBOLISM | 0/54 (0%) | 1/55 (1.8%) | ||
| HYPOTENSION | 0/54 (0%) | 1/55 (1.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Lenalidomide | Investigator's Choice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/54 (98.1%) | 52/55 (94.5%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 17/54 (31.5%) | 31/55 (56.4%) | ||
| LEUKOPENIA | 3/54 (5.6%) | 8/55 (14.5%) | ||
| LYMPHOPENIA | 1/54 (1.9%) | 5/55 (9.1%) | ||
| NEUTROPENIA | 23/54 (42.6%) | 18/55 (32.7%) | ||
| THROMBOCYTOPENIA | 13/54 (24.1%) | 17/55 (30.9%) | ||
| Cardiac disorders | ||||
| TACHYCARDIA | 3/54 (5.6%) | 1/55 (1.8%) | ||
| Ear and labyrinth disorders | ||||
| HYPOACUSIS | 0/54 (0%) | 3/55 (5.5%) | ||
| VERTIGO | 3/54 (5.6%) | 1/55 (1.8%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL DISTENSION | 4/54 (7.4%) | 1/55 (1.8%) | ||
| ABDOMINAL PAIN | 10/54 (18.5%) | 12/55 (21.8%) | ||
| CONSTIPATION | 16/54 (29.6%) | 16/55 (29.1%) | ||
| DIARRHOEA | 18/54 (33.3%) | 16/55 (29.1%) | ||
| DRY MOUTH | 7/54 (13%) | 3/55 (5.5%) | ||
| DYSPEPSIA | 3/54 (5.6%) | 3/55 (5.5%) | ||
| NAUSEA | 10/54 (18.5%) | 23/55 (41.8%) | ||
| STOMATITIS | 1/54 (1.9%) | 5/55 (9.1%) | ||
| VOMITING | 9/54 (16.7%) | 11/55 (20%) | ||
| General disorders | ||||
| ASTHENIA | 10/54 (18.5%) | 13/55 (23.6%) | ||
| CHILLS | 4/54 (7.4%) | 2/55 (3.6%) | ||
| FATIGUE | 19/54 (35.2%) | 16/55 (29.1%) | ||
| NON-CARDIAC CHEST PAIN | 4/54 (7.4%) | 1/55 (1.8%) | ||
| OEDEMA PERIPHERAL | 9/54 (16.7%) | 10/55 (18.2%) | ||
| PYREXIA | 16/54 (29.6%) | 18/55 (32.7%) | ||
| Infections and infestations | ||||
| BRONCHITIS | 6/54 (11.1%) | 0/55 (0%) | ||
| LOWER RESPIRATORY TRACT INFECTION | 3/54 (5.6%) | 6/55 (10.9%) | ||
| LUNG INFECTION | 0/54 (0%) | 3/55 (5.5%) | ||
| NASOPHARYNGITIS | 3/54 (5.6%) | 1/55 (1.8%) | ||
| PNEUMONIA | 1/54 (1.9%) | 3/55 (5.5%) | ||
| RHINITIS | 3/54 (5.6%) | 4/55 (7.3%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 5/54 (9.3%) | 5/55 (9.1%) | ||
| URINARY TRACT INFECTION | 3/54 (5.6%) | 4/55 (7.3%) | ||
| Injury, poisoning and procedural complications | ||||
| DRUG PRESCRIBING ERROR | 5/54 (9.3%) | 1/55 (1.8%) | ||
| Investigations | ||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 3/54 (5.6%) | 1/55 (1.8%) | ||
| BLOOD ALKALINE PHOSPHATASE INCREASED | 0/54 (0%) | 4/55 (7.3%) | ||
| BLOOD CREATININE INCREASED | 2/54 (3.7%) | 4/55 (7.3%) | ||
| BLOOD LACTATE DEHYDROGENASE INCREASED | 0/54 (0%) | 3/55 (5.5%) | ||
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 0/54 (0%) | 3/55 (5.5%) | ||
| NEUTROPHIL COUNT DECREASED | 0/54 (0%) | 7/55 (12.7%) | ||
| PLATELET COUNT DECREASED | 0/54 (0%) | 9/55 (16.4%) | ||
| WHITE BLOOD CELL COUNT DECREASED | 0/54 (0%) | 5/55 (9.1%) | ||
| Metabolism and nutrition disorders | ||||
| DECREASED APPETITE | 8/54 (14.8%) | 15/55 (27.3%) | ||
| HYPERGLYCAEMIA | 3/54 (5.6%) | 6/55 (10.9%) | ||
| HYPOCALCAEMIA | 1/54 (1.9%) | 3/55 (5.5%) | ||
| HYPOKALAEMIA | 6/54 (11.1%) | 10/55 (18.2%) | ||
| HYPOPHOSPHATAEMIA | 1/54 (1.9%) | 3/55 (5.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 7/54 (13%) | 5/55 (9.1%) | ||
| BACK PAIN | 3/54 (5.6%) | 8/55 (14.5%) | ||
| MUSCLE SPASMS | 4/54 (7.4%) | 2/55 (3.6%) | ||
| MUSCULAR WEAKNESS | 3/54 (5.6%) | 1/55 (1.8%) | ||
| MUSCULOSKELETAL PAIN | 3/54 (5.6%) | 0/55 (0%) | ||
| MYALGIA | 4/54 (7.4%) | 4/55 (7.3%) | ||
| PAIN IN EXTREMITY | 6/54 (11.1%) | 5/55 (9.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| DIFFUSE LARGE B-CELL LYMPHOMA | 3/54 (5.6%) | 1/55 (1.8%) | ||
| TUMOUR FLARE | 5/54 (9.3%) | 0/55 (0%) | ||
| Nervous system disorders | ||||
| DIZZINESS | 3/54 (5.6%) | 5/55 (9.1%) | ||
| DYSGEUSIA | 2/54 (3.7%) | 3/55 (5.5%) | ||
| HEADACHE | 3/54 (5.6%) | 6/55 (10.9%) | ||
| HYPOAESTHESIA | 3/54 (5.6%) | 1/55 (1.8%) | ||
| LETHARGY | 4/54 (7.4%) | 1/55 (1.8%) | ||
| PERIPHERAL SENSORY NEUROPATHY | 2/54 (3.7%) | 5/55 (9.1%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 4/54 (7.4%) | 5/55 (9.1%) | ||
| DEPRESSION | 3/54 (5.6%) | 3/55 (5.5%) | ||
| INSOMNIA | 3/54 (5.6%) | 2/55 (3.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 13/54 (24.1%) | 10/55 (18.2%) | ||
| DYSPNOEA | 6/54 (11.1%) | 12/55 (21.8%) | ||
| EPISTAXIS | 0/54 (0%) | 3/55 (5.5%) | ||
| OROPHARYNGEAL PAIN | 2/54 (3.7%) | 4/55 (7.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| DRY SKIN | 3/54 (5.6%) | 0/55 (0%) | ||
| ERYTHEMA | 3/54 (5.6%) | 1/55 (1.8%) | ||
| PRURITUS | 3/54 (5.6%) | 3/55 (5.5%) | ||
| PRURITUS GENERALISED | 1/54 (1.9%) | 3/55 (5.5%) | ||
| RASH | 9/54 (16.7%) | 2/55 (3.6%) | ||
| RASH MACULO-PAPULAR | 3/54 (5.6%) | 1/55 (1.8%) | ||
| Vascular disorders | ||||
| HYPOTENSION | 3/54 (5.6%) | 3/55 (5.5%) | ||
Limitations/Caveats
On 29 January 2013 the Stage 1 portion of the study was met and enrollment stopped. The Stage 1 results as assessed by the IRAC demonstrated that neither subtype met the prespecified requirement to be further studied in Stage 2.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Results Point of Contact
| Name/Title | Anne McClain |
|---|---|
| Organization | Celgene |
| Phone | 1-888-260-1599 |
| clinicaltrialdisclosure@celgene.com |
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01197560
Other Study ID Numbers:
- CC-5013-DLC-001
First Posted:
Sep 9, 2010
Last Update Posted:
Nov 25, 2019
Last Verified:
Nov 1, 2019