Diffuse Large B-cells Non-Hodgkin LymphomaPhase 2NCT02955823
A Phase II Study of the FIL on Elderly Frail Patients With DLBCL
A Phase 2 study testing Rituximab-Dexamethasone-Lenalidomide in people with Diffuse Large B-cells Non-Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 18 sites in Italy.
Trial summary
A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Diffuse Large B-cells Non-Hodgkin Lymphoma
- What is being tested?
- Rituximab-Dexamethasone-Lenalidomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 18 sitesItaly
- Study dates
- Sep 2016to 24 Nov 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
- Age ≥ 70 years
- Previously untreated
- CGA assessment performed before starting treatment
- FRAIL patients defined as follows
- Age > 80 years (with UNFIT profile):
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- ADL ≥ 5 residual functions and/or IADL ≥ 6 residual functions and/or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2
- Age < 80 (ONLY one of the following criteria):
- ADL ≤ 4 residual functions IADL ≤ 5 residual functions CIRS: 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2
- Ann Arbor Stage I - IV (Appendix F)
- At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
- ECOG performance status of 0- 3 (Appendix E)
- No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
- Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:
- Hemoglobin > 10 g/dL
- WBC > 2500/mmc with PMN > 1000/ mmc
- Platelets count ≥ 75000/mmc
- Creatinine clearance ≥ 10 mL/min
- Ability and willingness to comply with the study protocol procedure
- Life expectancy > 6 months
- Patients must give written informed consent.
- Male subjects must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
Who cannot join
- Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
- Previous exposure to cytotoxic agents
- Suspect or clinical evidence of CNS involvement by lymphoma
- Contraindication to the use of Rituximab or of Lenalidomide
- HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided.
- HIV positivity
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- Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
- Any history of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
- AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL
- Creatinine clearance < 10 mL/min
- Evidence of any severe active acute or chronic infection
- Severe cardiac dysfunction (NYHA grade III-IV)
- Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
- Absence of caregivers in non-autonomous patients
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Italy18 sites
Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
Ancona
A.O. Spedali Civili di Brescia - Ematologia
Brescia
IRCCS AOU S. Martino - IST - Clinica Ematologica
Genova
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
Meldola, Forlì-Cesena
Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia
Messina
Ospedale Dell'Angelo - U.O. Ematologia
Mestre, Venezia
ASST Grande Ospedale Metropolitano Niguarda
Milan
Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
Modena
I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
Padova
AOU di Parma - U.O. Complessa di Ematologia
Parma
Ospedale Guglielmo da Saliceto - U.O.Ematologia
Piacenza, 29121
Ospedale delle Croci - Ematologia
Ravenna
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia
Reggio Emilia, Reggio Emilia
Ospedale degli Infermi di Rimini - U.O. di Ematologia
Rimini
Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare
Roma
Univ. Perugia Sede Terni - Oncoematologia
Terni
A.O. C. Panico - U.O.C Ematologia e Trapianto
Tricase, Lecce
Ospedale ULSS 6 di Vicenza - Ematologia
Vicenza
About this study
Official title: A Combination of Lenalidomide and Rituximab as Front Line Therapy for the Treatment of Elderly Frail Patients Evaluated in CGA With Diffuse Large B-cells Non-Hodgkin Lymphoma. A Phase II Study of the Fondazione Italiana Linfomi (FIL)
A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma.
Read the detailed description
This is a prospective, multicenter, single arm, phase II trial in elderly patients (≥ 70 years) affected by DLBCL defined as frail according to CGA and previously untreated.
The primary endpoint is to evaluate the efficacy of the R2 (Revlimid+Rituximab) combination in first line DLBCL patients not candidate for the standard R-CHOP (or R-CHOP like) treatments due to the frail status.
- Being tested
- Rituximab-Dexamethasone-Lenalidomide
- Keywords
- B cell Lymphoma, non-Hodgkin Lymphoma, Elderly patients
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab-Dexamethasone-LenalidomideDrug
- st CYCLE: Rituximab 375 mg/m2 i.v. on days 1,8,15; Dexamethasone 5 mg p.o. on days 1,8,15,22; Lenalidomide 15 mg/day p.o. day 2-22
- nd-4th CYCLE: Rituximab 375 mg/m2 i.v. on day 1; Lenalidomide 20 mg/day p.o. from day 2 to day 22 At the end of 4th CYCLE disease restaging: - if ≥ PR continues with the 5th and 6th cycle: Rituximab 375 mg/m2 i.v. on day 1, Lenalidomide 20 mg /day p.o. day 2-22
- if <PR stops the treatment, only follow-up At the end of the 6th CYCLE disease restaging: - if ≥ PR continues with beyond the 6th cycle with Lenalidomide 10mg dd1-21q28 until cycle 12th
- if <PR stops the treatment, only follow-up Then, accordingly response rate after the sixth cycle assessment(≥ PR) lenalidomide will be continued at 10 mg dd1-21q28 until 12th cycle or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| 1 arm for all patient: Ritux-Dexame-Lena | Experimental | Rituximab-Dexamethasone-Lenalidomide Receives: Drug: Rituximab-Dexamethasone-Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Overall response rate (ORR) is defined as the proportion of patients with complete and partial response respectively according to Cheson 2014 (Appendix K).
The ORR rate will be evaluated both on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders.
Response of R2 will be calculated for the EP according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014; patients will be categorized into Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Non Responders (NR).
Measured: 48 months
Safety: clinical relevant toxicity
Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.
Measured: 48 months
Secondary outcomes (5)
CR
- Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.
Measured: 48 months
OS
- Overall Survival (OS) will be defined as the time between the date of enrolment and the date of death from any cause. Patients who have not died at the time of the final analysis and patients who are lost to follow up will be censored at the date of the last contact.
Measured: 54 months
PFS
- Progression Free Survival (PFS) will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause. Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date.
Time to event data (PFS, OS) will be estimated using the Kaplan-Meier method. The curves will be plotted and the 95% confidence interval for median time will be calculated.
Measured: 54 months
EFS
- Event-Free Survival (EFS), (time to treatment failure) is measured from the time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death). Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date.
Measured: 54 months
Quality of life
- Patients will assess their health-related quality of life (HRQoL) using two validated questionnaires: the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) and the Quality of life (EORTC-QLQ-C30). Items for inclusion in the lymphoma subscale were selected on the basis of symptom relevance, disease specificity, and clinical relevance.
Measured: 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2016 (estimated)
- Study startSep 2016
- Primary completion22 Sep 2020
- Study completion24 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cells Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Italiana Linfomi - ETS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guido Gini, MD, Principal investigator, Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02955823
- Sponsor's protocol ID
- FIL_ReRi
- Status last verified
- Dec 2022
- First submitted
- 2 Nov 2016
- Last updated
- 23 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Gini G, Tani M, Tucci A, Marcheselli L, Cesaretti M, Bellei M, Pascarella A, Ballerini F, Petrini M, Merli F, Olivieri A, Lanza F, Annibali O, Zilioli VR, Liberati AM, Tisi MC, Arcari A, Marino D, Musuraca G, Pavone V, Fabbri A, Pozzi S, Mannina D, Plenteda C, Celli M, Luminari S. Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study. Blood. 2023 Oct 26;142(17):1438-1447. doi: 10.1182/blood.2022019173.
PubMed 37418685
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combination of Lenalidomide and Rituximab as Front Line Therapy for the Treatment of Elderly Frail Patients Evaluated in CGA With Diffuse Large B-cells Non-Hodgkin Lymphoma. A Phase II Study of the Fondazione Italiana Linfomi (FIL)
- ClinicalTrials.gov ID
- NCT02955823
- Acronym / sponsor ID
- FIL_ReRi
- Keywords
- B cell Lymphoma, non-Hodgkin Lymphoma, Elderly patients
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Fondazione Italiana Linfomi - ETSUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- 22 Sep 2020 (actual)
- Study completion
- 24 Nov 2022 (actual)
- First posted
- 4 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma.
Detailed description
This is a prospective, multicenter, single arm, phase II trial in elderly patients (≥ 70 years) affected by DLBCL defined as frail according to CGA and previously untreated.
The primary endpoint is to evaluate the efficacy of the R2 (Revlimid+Rituximab) combination in first line DLBCL patients not candidate for the standard R-CHOP (or R-CHOP like) treatments due to the frail status.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 arm for all patient: Ritux-Dexame-Lena | Experimental | Drug: Rituximab-Dexamethasone-LenalidomideRituximab-Dexamethasone-Lenalidomide |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (22 listed)
- Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
- Age ≥ 70 years
- Previously untreated
- CGA assessment performed before starting treatment
- FRAIL patients defined as follows
Key exclusion criteria (14 listed)
- Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
- Previous exposure to cytotoxic agents
- Suspect or clinical evidence of CNS involvement by lymphoma
- Contraindication to the use of Rituximab or of Lenalidomide
- HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab-Dexamethasone-Lenalidomide1. st CYCLE: Rituximab 375 mg/m2 i.v. on days 1,8,15; Dexamethasone 5 mg p.o. on days 1,8,15,22; Lenalidomide 15 mg/day p.o. day 2-22 2. nd-4th CYCLE: Rituximab 375 mg/m2 i.v. on day 1; Lenalidomide 20 mg/day p.o. from day 2 to day 22 At the end of 4th CYCLE disease restaging: - if ≥ PR continues with the 5th and 6th cycle: Rituximab 375 mg/m2 i.v. on day 1, Lenalidomide 20 mg /day p.o. day 2-22 * if <PR stops the treatment, only follow-up At the end of the 6th CYCLE disease restaging: - if ≥ PR continues with beyond the 6th cycle with Lenalidomide 10mg dd1-21q28 until cycle 12th * if <PR stops the treatment, only follow-up Then, accordingly response rate after the sixth cycle assessment(≥ PR) lenalidomide will be continued at 10 mg dd1-21q28 until 12th cycle or unacceptable toxicity. | Drug | 1 arm for all patient: Ritux-Dexame-Lena |
Primary outcome
ORR
Time frame: 48 months
Overall response rate (ORR) is defined as the proportion of patients with complete and partial response respectively according to Cheson 2014 (Appendix K). The ORR rate will be evaluated both on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders. Response of R2 will be calculated for the EP according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014; patients will be categorized into Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Non Responders (NR).
Safety: clinical relevant toxicity
Time frame: 48 months
Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.
5 secondary outcomes
CR
Time frame: 48 months
OS
Time frame: 54 months
PFS
Time frame: 54 months
EFS
Time frame: 54 months
Quality of life
Time frame: 54 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Derived from this study: PubMed 37418685Gini G, Tani M, Tucci A, Marcheselli L, Cesaretti M, Bellei M, Pascarella A, Ballerini F, Petrini M, Merli F, Olivieri A, Lanza F, Annibali O, Zilioli VR, Liberati AM, Tisi MC, Arcari A, Marino D, Musuraca G, Pavone V, Fabbri A, Pozzi S, Mannina D, Plenteda C, Celli M, Luminari S. Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study. Blood. 2023 Oct 26;142(17):1438-1447. doi: 10.1182/blood.2022019173.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guido Gini, MD principal investigator
Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab-Dexamethasone-Lenalidomide in people with Diffuse Large B-cells Non-Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 18 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02955823, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2022.