Metronomic Chemotherapy in Elderly Non-fit Patients With Aggressive B-Cell Lymphomas

NCT03161054 | Completed Phase 2

• 1 other identifier: FIL_DEVEC
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 10

Brief Summary

This is a phase II study of metronomic chemotherapy in elderly non-fit patients (\>65 years) with aggressive B-Cell lymphomas

Conditions

Aggressive Non-Hodgkin Lymphoma

Keywords

Metronomic Chemotherapy; Elderly non-fit patients; Aggressive B-Cell lymphomas

Outcome Measures

Primary Outcomes (2)

• Complete Remission Rate (CRR)

  The primary efficacy endpoint is defined in terms of complete response (CR), including complete response unconfirmed (CRu), according to Recommendations of an International Workshop to Standardise Response Criteria for Non-Hodgkin´s Lymphomas.

  30 months

• Incidence of adverse events

  The primary safety endpoint is defined as incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

  30 months

Secondary Outcomes (7)

• Overall response rate (ORR)

  30 months

• Clinical Benefit

  30 months

• Progression Free Survival (PFS)

  36

• Event Free Survival (EFS)

  36

• Disease Free Survival (DFS)

  36

Study Arms (1)

One arm for all patient

EXPERIMENTAL

Induction phase: Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after \>6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy. Super-frail patients will not receive etoposide during cycles 1 and 2. Maintenance Phase: Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles. Post Maintenance Phase: Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance

Drug: Prednisone; Drug: Vinorelbine; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Rituximab

Interventions

Prednisone DRUG

Induction Phase: Prednisone (Deltacortene) 25 mg /day will be orally administered from day 1 to day 28 only in cycle 1 From cycle 2 to 6 reduce to three times a week (after breakfast). Maintenance Phase: Prednisone 25 mg/day will be orally administered twice a week continuously (after breakfast). Post Maintenance Phase: Prednisone 25 mg/day will be orally administered twice a week continuously (after breakfast).

One arm for all patient

Vinorelbine DRUG

Induction Phase: Vinorelbine 30 mg/day will be orally administered three times a week, 3 weeks on and 1 week off (after breakfast). Maintenance Phase: Vinorelbine 30 mg/day will be orally administered three times a week, 3 weeks on and 1 week off (after breakfast). Post Maintenance Phase: vinorelbine 30 mg/day will be orally administered three times a week, 3 weeks on and 1 week off (after breakfast).

One arm for all patient

Etoposide DRUG

Induction Phase Etoposide: 50 mg/day will be orally administered from day 1 to day 14 (before lunch); Superfrail patients only from cycle 3, 50 mg/day, from day 1 to day 7

One arm for all patient

Cyclophosphamide DRUG

Induction Phase: Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 21 (after dinner). Maintenance Phase: 50 mg/day will be orally administered from day 1 to day 14 (after dinner).

One arm for all patient

Rituximab DRUG

Induction Phase: Rituximab: 375 mg/m2 will be administered by IV infusion up to four infusions on days 8, 15, 22, 29, only in patients suitable for infusion treatment and relapsed after \>6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of Rituximab will not repeat it during the metronomic therapy.

One arm for all patient

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of aggressive Non-Hodgkin Lymphomas (NHLs) including:
• LBCL1
• DLBCL;
• Grade IIIb follicular lymphoma;
• BL1;
• B-Cell unclassifiable lymphomas with features intermediate between DLBCL and BL or between DLBCL and Hodgkin's lymphoma (HL)35;
• High grade B-cell lymphomas1
• Age \>65 years
• Unfit or frail patients (the latest defined, for the purpose of this study, as those who have a maximum of 1 frail factor) according to the multidimensional geriatric evaluation model of the elderly platform of the FIL, who relapsed/progressed after one or maximum two previous lines of treatment or
• "Super-frail" elderly patients at disease onset: eligible super-frail patients are defined, for the purpose of this study, as those who have a maximum of 2 frail factors, according to the CGA adopted in the elderly platform of the FIL, among those below listed:
• ADL ≤ 4;
• IADL ≤ 5;
• Age ≥ 80 years;
• CIRS grade 3 or \>8 CIRS grade 2.
• Ann Arbor stage I bulky to IV

You may not qualify if:

• Patients who received more than two previous chemotherapy lines.
• Relapsed/refractory patients with fit profile.
• Fit, unfit, and frail patients at disease onset.
• Malabsorption syndrome or other diseases that affect the ability to swallow oral therapy.
• Concomitant malignancy requiring treatment (except non-melanoma skin cancers and in situ carcinoma of the uterine cervix).
• Presence of opportunistic infections in place.
• Seropositive for or active viral infection with hepatitis B virus (HBV):
• HBsAg positive;
• HBsAg negative, HBcAb positive with detectable viral DNA (Subjects who are HBsAg negative, HBcAb positive, but viral DNA negative are eligible.
• Seropositive and active infection for hepatitis C virus (subjects who are HCV-RNA negative are eligible).
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
• Impossibility to give written informed consent.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (10)

A.O. Spedali Civili di Brescia - Ematologia

Brescia, Italy

Location

Ospedale di Castelfranco Veneto - Ematologia

Castelfranco Veneto, Italy

Location

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

Meldola, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, Italy

Location

Ospedale delle Croci - Ematologia

Ravenna, Italy

Location

Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS c/o CORE (II piano) - Ematologia

Reggio Emilia, Italy

Location

AO Sant'Andrea - Ematologia

Roma, Italy

Location

Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

Sassuolo, Italy

Location

AOU Senese - U.O.C. Ematologia

Siena, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, Italy

Location

MeSH Terms

Interventions

Prednisone; Vinorelbine; Etoposide; Cyclophosphamide; Rituximab

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Francesco Merli, MD

  AUSL - IRCCS Arcispedale Santa Maria Nuova viale Risorgimento 80 42123, Reggio Emilia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: phase II, multicentre, non-randomized study, single arm study

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: May 19, 2017
• Study Start: September 12, 2017
• Primary Completion: April 22, 2020
• Study Completion: June 21, 2021
• Last Updated: December 20, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (10)