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A Phase II Study of the FIL on Elderly Frail Patients With DLBCL

Primary Purpose

Diffuse Large B-cells Non-Hodgkin Lymphoma

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Rituximab-Dexamethasone-Lenalidomide
Sponsored by
Fondazione Italiana Linfomi - ETS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cells Non-Hodgkin Lymphoma focused on measuring B cell Lymphoma, non-Hodgkin Lymphoma, Elderly patients

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
  2. Age ≥ 70 years
  3. Previously untreated
  4. CGA assessment performed before starting treatment

  5. FRAIL patients defined as follows

    Age > 80 years (with UNFIT profile):

    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

  6. Ann Arbor Stage I - IV (Appendix F)
  7. At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
  8. ECOG performance status of 0- 3 (Appendix E)
  9. No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.

  10. 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
  11. Ability and willingness to comply with the study protocol procedure
  12. Life expectancy > 6 months
  13. Patients must give written informed consent.
  14. 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.

Exclusion Criteria:

  1. Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
  2. Previous exposure to cytotoxic agents
  3. Suspect or clinical evidence of CNS involvement by lymphoma
  4. Contraindication to the use of Rituximab or of Lenalidomide
  5. 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.
  6. HIV positivity
  7. Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
  8. 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
  9. AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL
  10. Creatinine clearance < 10 mL/min
  11. Evidence of any severe active acute or chronic infection
  12. Severe cardiac dysfunction (NYHA grade III-IV)
  13. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
  14. Absence of caregivers in non-autonomous patients

Sites / Locations

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
  • A.O. C. Panico - U.O.C Ematologia e Trapianto
  • Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia
  • Ospedale Dell'Angelo - U.O. Ematologia
  • Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
  • A.O. Spedali Civili di Brescia - Ematologia
  • IRCCS AOU S. Martino - IST - Clinica Ematologica
  • Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia
  • ASST Grande Ospedale Metropolitano Niguarda
  • Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
  • I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
  • AOU di Parma - U.O. Complessa di Ematologia
  • Ospedale Guglielmo da Saliceto - U.O.Ematologia
  • Ospedale delle Croci - Ematologia
  • Ospedale degli Infermi di Rimini - U.O. di Ematologia
  • Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare
  • Univ. Perugia Sede Terni - Oncoematologia
  • Ospedale ULSS 6 di Vicenza - Ematologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1 arm for all patient: Ritux-Dexame-Lena

Arm Description

Rituximab-Dexamethasone-Lenalidomide

Outcomes

Primary Outcome Measures

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).
Safety: clinical relevant toxicity
Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.

Secondary Outcome Measures

CR
1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.
OS
2) 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.
PFS
3) 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.
EFS
4) 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.
Quality of life
5) 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.

Full Information

First Posted
November 2, 2016
Last Updated
December 22, 2022
Sponsor
Fondazione Italiana Linfomi - ETS
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1. Study Identification

Unique Protocol Identification Number
NCT02955823
Brief Title
A Phase II Study of the FIL on Elderly Frail Patients With DLBCL
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)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
September 22, 2020 (Actual)
Study Completion Date
November 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Italiana Linfomi - ETS

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cells Non-Hodgkin Lymphoma
Keywords
B cell Lymphoma, non-Hodgkin Lymphoma, Elderly patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 arm for all patient: Ritux-Dexame-Lena
Arm Type
Experimental
Arm Description
Rituximab-Dexamethasone-Lenalidomide
Intervention Type
Drug
Intervention Name(s)
Rituximab-Dexamethasone-Lenalidomide
Intervention Description
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.
Primary Outcome Measure Information:
Title
ORR
Description
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).
Time Frame
48 months
Title
Safety: clinical relevant toxicity
Description
Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.
Time Frame
48 months
Secondary Outcome Measure Information:
Title
CR
Description
1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.
Time Frame
48 months
Title
OS
Description
2) 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.
Time Frame
54 months
Title
PFS
Description
3) 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.
Time Frame
54 months
Title
EFS
Description
4) 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.
Time Frame
54 months
Title
Quality of life
Description
5) 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.
Time Frame
54 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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): 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. Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guido Gini, MD
Organizational Affiliation
Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
City
Meldola
State/Province
Forlì-Cesena
Country
Italy
Facility Name
A.O. C. Panico - U.O.C Ematologia e Trapianto
City
Tricase
State/Province
Lecce
Country
Italy
Facility Name
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia
City
Reggio nell'Emilia
State/Province
Reggio Emilia
Country
Italy
Facility Name
Ospedale Dell'Angelo - U.O. Ematologia
City
Mestre
State/Province
Venezia
Country
Italy
Facility Name
Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
City
Ancona
Country
Italy
Facility Name
A.O. Spedali Civili di Brescia - Ematologia
City
Brescia
Country
Italy
Facility Name
IRCCS AOU S. Martino - IST - Clinica Ematologica
City
Genova
Country
Italy
Facility Name
Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia
City
Messina
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
Country
Italy
Facility Name
Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
City
Modena
Country
Italy
Facility Name
I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
City
Padova
Country
Italy
Facility Name
AOU di Parma - U.O. Complessa di Ematologia
City
Parma
Country
Italy
Facility Name
Ospedale Guglielmo da Saliceto - U.O.Ematologia
City
Piacenza
ZIP/Postal Code
29121
Country
Italy
Facility Name
Ospedale delle Croci - Ematologia
City
Ravenna
Country
Italy
Facility Name
Ospedale degli Infermi di Rimini - U.O. di Ematologia
City
Rimini
Country
Italy
Facility Name
Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare
City
Roma
Country
Italy
Facility Name
Univ. Perugia Sede Terni - Oncoematologia
City
Terni
Country
Italy
Facility Name
Ospedale ULSS 6 di Vicenza - Ematologia
City
Vicenza
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase II Study of the FIL on Elderly Frail Patients With DLBCL

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