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

NCT ID: NCT02955823

Last Updated: 2022-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2022-11-24

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.

Conditions

Diffuse Large B-cells Non-Hodgkin Lymphoma

Keywords

B cell Lymphoma; non-Hodgkin Lymphoma; Elderly patients

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 arm for all patient: Ritux-Dexame-Lena

Rituximab-Dexamethasone-Lenalidomide

Group Type: EXPERIMENTAL

Rituximab-Dexamethasone-Lenalidomide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guido Gini, MD

Role: PRINCIPAL_INVESTIGATOR

Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona

Locations

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

Tricase, Lecce, Italy

Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS - Ematologia

Reggio Emilia, Reggio Emilia, Italy

Ospedale Dell'Angelo - U.O. Ematologia

Mestre, Venezia, Italy

Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona

Ancona, , Italy

A.O. Spedali Civili di Brescia - Ematologia

Brescia, , Italy

IRCCS AOU S. Martino - IST - Clinica Ematologica

Genova, , Italy

Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia

Messina, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliero - Universitaria Policlinico di Modena - Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica

Modena, , Italy

I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1

Padua, , Italy

AOU di Parma - U.O. Complessa di Ematologia

Parma, , Italy

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, , Italy

Ospedale delle Croci - Ematologia

Ravenna, , Italy

Ospedale degli Infermi di Rimini - U.O. di Ematologia

Rimini, , Italy

Policlinico Universitario Campus Bio-Medico - Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare

Roma, , Italy

Univ. Perugia Sede Terni - Oncoematologia

Terni, , Italy

Ospedale ULSS 6 di Vicenza - Ematologia

Vicenza, , Italy

Countries

Italy

References

Gini G, Tani M, Tucci A, Marcheselli L, Cesaretti M, Bellei M, Pascarella A, Ballerini F, Petrini M, Merli F, Olivieri A, Lanza F, Annibali O, Zilioli VR, Liberati AM, Tisi MC, Arcari A, Marino D, Musuraca G, Pavone V, Fabbri A, Pozzi S, Mannina D, Plenteda C, Celli M, Luminari S. Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study. Blood. 2023 Oct 26;142(17):1438-1447. doi: 10.1182/blood.2022019173.

Reference Type: DERIVED

PMID: 37418685 (View on PubMed)

Other Identifiers

FIL_ReRi

Identifier Type: -

Identifier Source: org_study_id