Clinical trial NCT02955823: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B-cells Non-Hodgkin Lymphoma
Keywords: B cell Lymphoma
non-Hodgkin Lymphoma
Elderly patients
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2016-11-04
Enrollment: 68
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: ORR
timeFrame: 48 months
measure: Safety: clinical relevant toxicity
timeFrame: 48 months
Secondary outcomes:
measure: CR
timeFrame: 48 months
measure: OS
timeFrame: 54 months
measure: PFS
timeFrame: 54 months
measure: EFS
timeFrame: 54 months
measure: Quality of life
timeFrame: 54 months
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
state: Forlì-Cesena
city: Tricase
country: Italy
facility: A.O. C. Panico - U.O.C Ematologia e Trapianto
state: Lecce
city: Reggio nell'Emilia
country: Italy
facility: Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia
state: Reggio Emilia
city: Mestre
country: Italy
facility: Ospedale Dell'Angelo - U.O. Ematologia
state: Venezia
city: Ancona
country: Italy
facility: Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia - Ematologia
city: Genova
country: Italy
facility: IRCCS AOU S. Martino - IST - Clinica Ematologica
city: Messina
country: Italy
facility: Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica
city: Padova
country: Italy
facility: I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
city: Parma
country: Italy
facility: AOU di Parma - U.O. Complessa di Ematologia
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - U.O.Ematologia
city: Ravenna
country: Italy
facility: Ospedale delle Croci - Ematologia
city: Rimini
country: Italy
facility: Ospedale degli Infermi di Rimini - U.O. di Ematologia
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare
city: Terni
country: Italy
facility: Univ. Perugia Sede Terni - Oncoematologia
city: Vicenza
country: Italy
facility: Ospedale ULSS 6 di Vicenza - Ematologia
Study officials:
affiliation: Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
name: Guido Gini, MD
role: PRINCIPAL_INVESTIGATOR
References: