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

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.

Study Overview

• Status: Completed
• Conditions: Diffuse Large B-cells Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Rituximab-Dexamethasone-Lenalidomide

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
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
  • Brescia, Italy
    • A.O. Spedali Civili di Brescia - Ematologia
  • Genova, Italy
    • IRCCS AOU S. Martino - IST - Clinica Ematologica
  • Messina, Italy
    • Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia
  • Milano, Italy
    • ASST Grande Ospedale Metropolitano Niguarda
  • Modena, Italy
    • Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
  • Padova, Italy
    • I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
  • Parma, Italy
    • AOU di Parma - U.O. Complessa di Ematologia
  • Piacenza, Italy, 29121
    • Ospedale Guglielmo da Saliceto - U.O.Ematologia
  • Ravenna, Italy
    • Ospedale delle Croci - Ematologia
  • Rimini, Italy
    • Ospedale degli Infermi di Rimini - U.O. di Ematologia
  • Roma, Italy
    • Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare
  • Terni, Italy
    • Univ. Perugia Sede Terni - Oncoematologia
  • Vicenza, Italy
    • Ospedale ULSS 6 di Vicenza - Ematologia
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
  • Lecce
    • Tricase, Lecce, Italy
      • A.O. C. Panico - U.O.C Ematologia e Trapianto
  • Reggio Emilia
    • Reggio nell'Emilia, Reggio Emilia, Italy
      • Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia
  • Venezia
    • Mestre, Venezia, Italy
      • Ospedale Dell'Angelo - U.O. Ematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 68 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1 arm for all patient: Ritux-Dexame-Lena; Rituximab-Dexamethasone-Lenalidomide

Drug: Rituximab-Dexamethasone-Lenalidomide; 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 2-22if if

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	48 months
Safety: clinical relevant toxicity	Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR	1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.	48 months
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.	54 months
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.	54 months
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.	54 months
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.	54 months

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi ONLUS
• Investigators: Principal Investigator: Guido Gini, MD, Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): September 22, 2020
• Study Completion (Actual): November 24, 2022

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 4, 2016

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Elderly patients; B cell Lymphoma; non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Rituximab
• Other Study ID Numbers: FIL_ReRi

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No