Diffuse Large B-cell Lymphoma
Conditions
Keywords
Lenalidomide, revlimid, large B-cell lymphoma, relapse
Brief summary
This phase II multi-institutional trial will explore the safety and efficacy of lenalidomide monotherapy given as maintenance therapy following salvage chemo-immunotherapy in patients with relapsed or refractory chemosensitive diffuse large B-cell lymphoma
Detailed description
Patients older than 65 years or younger but not eligible to high-dose chemotherapy and autologous stem cell transplantation with biopsy-proven diffuse large B-cell lymphoma relapsed to previous combination chemotherapy regimen ± rituximab, who achieved at least a partial response to second-line chemotherapy (ICE or DHAP/DHAOx ((D)examethasone (H)igh-dose (A)ra-C - cytarabine (P)latinol (cisplatin)) or MINE (Mesna Ifosfamide Mitoxantrone Etoposide) regimen) + rituximab will receive single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment until progression of disease. Dose reductions of study drug will be made in case of adverse events when reported as correlated and when clinically appropriate. One-year progression free survival (PFS) will be the primary endpoint and overall survival, response rate and toxicity will be the secondary endpoints. With the null hypothesis (P0) of 1-year PFS of 30%, this study will consider a satisfactory efficacy of lenalidomide worth of further investigation a P1 corresponding to a 1-yr PFS of 50% (that is an absolute increase of 20% in terms of 1-yr progression-free survival). Considering a standard type I error (α) of 0,05 and a power of 80% (Type 2 error of 20%) 47 patients will be necessary for the trial.
Interventions
DRUGLenalidomide
single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment after the end of second-line chemotherapy until progression of disease.
Sponsors
Celgene
IRCCS San Raffaele
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
* Age \> 65 years * Age \< 65 but not eligible to high-dose chemotherapy and autologous stem cell transplantation * Biopsy-proven DLBCL relapsed to previous combination chemotherapy regimen ± rituximab * PR (Partial Response) or CR (Complete Response) to second-line chemotherapy (ICE or DHAP/DHAOx or MINE regimen) + rituximab * ECOG (Eastern Cooperative Oncology Group) performance status score \< 4 * Female of childbearing potential (FCBP) must demonstrate to practice a proper contraception to avoid any pregnancy risk during the study and at least 28 days after the discontinuation of the study * Male subjects must agree to practice a proper contraception during any sexual contact with females childbearing potential
Exclusion criteria
* CNS (Central Nervous System) involvement * Prior ASCT * TTP (Time To Progression) \<6 months after first-line therapy * Use of experimental drugs during second-line salvage chemotherapy * Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus ) * Active infectious disease * HIV, HBV (Hepatitis B Virus) or HCV (Hepatitis C Virus) - positivity * Impaired liver function (Bilirubin \>2 x upper normal limit; ALT (alanine aminotransferase) /AST (aspartate aminotransferase) /GGT (γ-glutamyltransferase) \> 3 x upper normal limit) at one month from salvage chemotherapy conclusion * Impaired renal function (creatinine clearance \<50 ml/min) at one month from salvage chemotherapy conclusion * Absolute neutrophil count (ANC) \<1000/microL * Platelet count \<75.000 /mm3 * Hemoglobin \<9 g/dL * Non-co-operative behaviour or non-compliance * Psychiatric diseases or conditions that might impair the ability to give informed consent * Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year Progression-free Survival | 1-year | It is defined as the number of participants alive after 1 year from enrolment to progression or relapse of lymphoma (if post-induction disease status was PR (Partial Response) or CR (Complete Response), respectively). Patients alive at last follow-up will be censored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 5 years | Secondary measures to describe long term outcome of treatment -Progression free survival It is defined as the number of participants, on a 5 yrs follow up, free from disease progression |
| Progression | 5 years | Progression It is defined as the number of participants with disease recurrence observed on a 5 yrs follow up. |
| Duration of Response | 5 years | Secondary measures to describe long term outcome of treatment * Duration of response It is defined as the number of participants experiencing a PFS (Progression Free Survival) from study therapy longer than previous line of treatment |
| Overall Survival | 5 years | Secondary measures to describe long term outcome of treatment -Overall survival It is defined as the number of participants alive at 5ys from enrolment (death for any cause). Patients alive at last follow-up will be censored. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment after the end of second-line chemotherapy until progression of disease.
Lenalidomide: single-agent lenalidomide 25 mg once daily for 21 days out of 28, as maintenance treatment after the end of second-line chemotherapy until progression of disease. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Lenalidomide | — |
|---|---|---|
| Advanced stage of disease | 35 Participants | — |
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 39 Participants | — |
| Age, Categorical Between 18 and 65 years | 7 Participants | — |
| Age, Continuous | 72 years | — |
| Bone marrow infiltration | 6 Participants | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Score >=1 | 18 Participants | — |
| Extranodal disease | 29 Participants | — |
| Hepatitis viral infection Both | 3 Participants | — |
| Hepatitis viral infection Hepatitis B Virus | 7 Participants | — |
| Hepatitis viral infection Hepatitis C Virus | 2 Participants | — |
| Hepatitis viral infection None | 34 Participants | — |
| Increased LDH (lactate dehydrogenase) serum level | 21 Participants | — |
| International Prognostic Index High- 5-year survival of 26% | 5 Participants | — |
| International Prognostic Index High-Intermediate- 5-year survival of 43% | 12 Participants | — |
| International Prognostic Index Low- 5-year survival of 73% | 8 Participants | — |
| International Prognostic Index Low-Intermediate- 5-year survival of 51% | 21 Participants | — |
| Previous ASCT (Autologous Stem-Cell Transplantation) | 6 Participants | — |
| Previous Lines for Diffuse Large B Cell Lymphoma (DLBCL) treatment Rituximab Cyclophosphamide Hydroxydaunorubicin Oncovin Prednisone.(R-CHOP) | 38 Participants | — |
| Previous Lines for Diffuse Large B Cell Lymphoma (DLBCL) treatment Rituximab+methotrexate+Adriamycin+cyclophosphamide+Oncovin+prednisone+bleomycin(R-VACOP-MACOP-B | 8 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Italy | 46 Participants | — |
| Relapse Status First | 33 Participants | — |
| Relapse Status Second | 13 Participants | — |
| Response at time of trial registration Complete remission | 26 Participants | — |
| Response at time of trial registration Partial remission | 20 Participants | — |
| Salvage chemoimmunotherapy Anthracycline-based: CHOP | 6 Participants | — |
| Salvage chemoimmunotherapy Bendamustine | 5 Participants | — |
| Salvage chemoimmunotherapy Gemcitabine-oxaliplatin | 4 Participants | — |
| Salvage chemoimmunotherapy High-dose Cytarabine-based:DHAOx | 10 Participants | — |
| Salvage chemoimmunotherapy High-dose Cytarabine-based: DHAP | 10 Participants | — |
| Salvage chemoimmunotherapy High-dose Cytarabine-based: ESHAP | 3 Participants | — |
| Salvage chemoimmunotherapy High-dose Ifosfamide-based: ICE | 8 Participants | — |
| Sex: Female, Male Female | 19 Participants | — |
| Sex: Female, Male Male | 27 Participants | — |
| Systemic symptoms (B status) | 5 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 48 |
| other Total, other adverse events | 7 / 48 |
| serious Total, serious adverse events | 12 / 48 |
Outcome results
Primary
1-year Progression-free Survival
It is defined as the number of participants alive after 1 year from enrolment to progression or relapse of lymphoma (if post-induction disease status was PR (Partial Response) or CR (Complete Response), respectively). Patients alive at last follow-up will be censored.
Time frame: 1-year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide | 1-year Progression-free Survival | 31 Participants |
Secondary
Duration of Response
Secondary measures to describe long term outcome of treatment * Duration of response It is defined as the number of participants experiencing a PFS (Progression Free Survival) from study therapy longer than previous line of treatment
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide | Duration of Response | 29 Participants |
Secondary
Overall Survival
Secondary measures to describe long term outcome of treatment -Overall survival It is defined as the number of participants alive at 5ys from enrolment (death for any cause). Patients alive at last follow-up will be censored.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide | Overall Survival | 26 Participants |
Secondary
Progression
Progression It is defined as the number of participants with disease recurrence observed on a 5 yrs follow up.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide | Progression | 21 Participants |
Secondary
Progression Free Survival
Secondary measures to describe long term outcome of treatment -Progression free survival It is defined as the number of participants, on a 5 yrs follow up, free from disease progression
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide | Progression Free Survival | 25 Participants |