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

Fondazione Italiana Linfomi - ETS68 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diffuse Large B-cells Non-Hodgkin Lymphoma

Interventions

Rituximab-Dexamethasone-LenalidomideDRUG

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.

Eligibility

Sex: ALLMin age: 70 Years

Medical Language ↔ Plain English

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

Locations (18)

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia

Meldola, Forlì-Cesena, Italy

A.O. C. Panico - U.O.C Ematologia e Trapianto

Outcomes

Primary Outcomes

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).

Time frame: 48 months

Safety: clinical relevant toxicity

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

Time frame: 48 months

Secondary Outcomes

1\) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.

Time frame: 48 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.

Time frame: 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.

Data from ClinicalTrials.gov

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