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

• ClinicalTrials.gov Identifier: NCT02955823
• Recruitment Status: Completed
• First Posted: November 4, 2016
• Last Update Posted: December 23, 2022
• Sponsor: Fondazione Italiana Linfomi - ETS
• Information provided by (Responsible Party): Fondazione Italiana Linfomi - ETS

Tracking Information

• First Submitted Date: November 2, 2016
• First Posted Date: November 4, 2016
• Last Update Posted Date: December 23, 2022
• Study Start Date: September 2016
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2016)

• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 13, 2018)

• CR [ Time Frame: 48 months ]
  1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.
• OS [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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.

Original Secondary Outcome Measures (submitted: November 2, 2016)

• CR [ Time Frame: 48 months ]
  1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.
• OS [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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 [ Time Frame: 54 months ]
  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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Large B-cells Non-Hodgkin Lymphoma

Intervention

Drug: Rituximab-Dexamethasone-Lenalidomide

1. 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.

Study Arms

Experimental: 1 arm for all patient: Ritux-Dexame-Lena

Rituximab-Dexamethasone-Lenalidomide

Intervention: Drug: Rituximab-Dexamethasone-Lenalidomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 2, 2016): 68
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 24, 2022
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT02955823
• Other Study ID Numbers: FIL_ReRi
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fondazione Italiana Linfomi - ETS
• Original Responsible Party: Same as current
• Current Study Sponsor: Fondazione Italiana Linfomi - ETS
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Guido Gini, MD; Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona

• PRS Account: Fondazione Italiana Linfomi - ETS
• Verification Date: December 2022