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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03161054
Recruitment Status : Recruiting
First Posted : May 19, 2017
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

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

Condition or disease Intervention/treatment Phase
Aggressive Non-Hodgkin Lymphoma Drug: Prednisone Drug: Vinorelbine Drug: Etoposide Drug: Cyclophosphamide Drug: Rituximab Phase 2

Detailed Description:

Patients eligible for the study will receive 6 courses (q 28 days) of the DEVEC combination, according to the following schedule:

  • DE: Prednisone (Deltacortene) 25 mg /day will be orally administered from day 1 to day 28 only in cycle 1 From cycle 2 to 6 it is reduced to three times a week (after breakfast, MON, WED, FRI)
  • V: Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI).
  • E: Etoposide 50 mg/day will be orally administered from day 1 to day 14 (before lunch).
  • C: Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 21 (after dinner).
  • 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 had received at least 5 doses of Rituximab will not repeat it during the metronomic therapy.

Super-frail patients will not receive etoposide during cycles 1 and 2; etoposide will be included in the treatment schedule starting from cycle 3 at reduced dose (50 mg/day, from day 1 to day 7) only in patients who in cycles 1 and 2 didn't experience hematological toxicity >G2 and/or non-hematological toxicity >G1.

Patients in CR, CRu, PR and SD after 2 cycles will continue with additional 4 courses. At the end of the induction phase patients in CR, CRu and PR (and also in SD at discretion of local investigator) will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles, according to the following schedule:

  • Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 14 (after dinner).
  • Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI).
  • Prednisone 25 mg/day will be orally administered twice a week (after breakfast, MON, FRI).

Patients in CR/CRu at the EOT can continue with a post-maintenance phase at discretion of the local investigator up to 12 months, progression or inacceptable toxicity, according to following schedule:

  • Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI).
  • Prednisone 25 mg/day will be orally administered twice a week (after breakfast, MON, FRI).

Patients with evidence of Progressive Disease (PD) at any point will stop treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Intervention Model Description: phase II, multicentre, non-randomized study, single arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Metronomic Chemotherapy in Elderly Non-fit Patients (>65 Years) With Aggressive B-Cell Lymphomas
Actual Study Start Date : September 12, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: One arm for all patient

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

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).


Drug: Vinorelbine

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).


Drug: Etoposide
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

Drug: Cyclophosphamide

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).


Drug: Rituximab
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.




Primary Outcome Measures :
  1. Complete Remission Rate (CRR) [ Time Frame: 30 months ]
    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.

  2. Incidence of adverse events [ Time Frame: 30 months ]
    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


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 30 months ]
    ORR, defined as the proportion of patients who achieved a CR (including CRu) or a PR.

  2. Clinical Benefit [ Time Frame: 30 months ]
    Defined as the percentage of patients who achieved a CR (including CRu), a PR and a SD.

  3. Progression Free Survival (PFS) [ Time Frame: 36 ]
    defined as the time from registration to the first occurrence of progression or relapse or death for any cause other causes than lymphoma, or the date of last follow-up in censored patients.

  4. Event Free Survival (EFS) [ Time Frame: 36 ]
    EFS, defined as the time from registration until: early withdrawal, less than CRu, relapse or progression or death by other causes than lymphoma in patients who achieved CR or CRu after the EOI phase.

  5. Disease Free Survival (DFS) [ Time Frame: 36 ]
    DFS: calculated for patients in CR/CRu after induction phase, from the date of response/end treatment until relapse, death by other causes than lymphoma or last follow-up in censored patients.

  6. Overall Survival (OS) [ Time Frame: 36 ]
    OS, calculated from the date of registration until death for any cause or last follow-up in censored patients.

  7. Patient-Reported Outcome (PRO) [ Time Frame: 36 ]
    PRO per European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QLQ-30) questionnaire



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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;
    • 1 CIRS grade 3 or >8 CIRS grade 2.
  • Ann Arbor stage I bulky to IV
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Life expectancy >1-2 months.
  • Adequate renal function (creatinine ≤ 2 mg/dl, unless secondary to lymphoma).
  • Adequate liver function (bilirubin ≤ 2 mg/dl, unless secondary to lymphoma).
  • Absolute neutrophil count (ANC) ≥1500 cells/mmc and platelets ≥ 50,000 cells/mmc, haemoglobin ≥ 9 gr/dl, unless cytopenia is related to bone marrow involvement by lymphoma.
  • Availability of adequate care by family members or other caregivers.
  • Written informed consent signature.
  • Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 3 months following the end or the discontinuation from the study treatment even if he has undergone a successful vasectomy.

Exclusion Criteria:

  • 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):

    1. HBsAg positive;
    2. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03161054


Contacts
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Contact: Uffici Studi FIL 0039 0131 206071 segreteria@filinf.it
Contact: Elena Borgo 0039 0131 206288 eborgo@filinf.it

Locations
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Italy
Università Politecnica delle Marche - Clinica di Ematologia Not yet recruiting
Ancona, Italy
Contact: Guido Gini, MD       guido.gini@ospedaliriuniti.marche.it   
Principal Investigator: Guido Gini, MD         
AOU Policlinico Consorziale - U.O. Ematologia con Trapianto Not yet recruiting
Bari, Italy
Contact: Giorgina Specchia, MD       giorgina.specchia@uniba.it   
Principal Investigator: Giorgina Specchia, MD         
IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia Not yet recruiting
Bari, Italy
Contact: Attilio Guarini, MD       attilioguarini@oncologico.bari.it   
Principal Investigator: Attilio Guarini, MD         
A.O. Spedali Civili di Brescia - Ematologia Not yet recruiting
Brescia, Italy
Contact: Alessandra Tucci, MD       alessandra.tucci@asst-spedalicivili.it   
Principal Investigator: Alessandra Tucci, MD         
Ospedale Antonio Perrino - U.O. Ematologia Not yet recruiting
Brindisi, Italy
Contact: Angela Maria Melpignano, MD       angelamelpignano@gmail.com   
Principal Investigator: Angela Maria Melpignano, MD         
Università Cattolica - Ematologia Not yet recruiting
Campobasso, Italy
Contact: Sergio Storti, MD       sergio.storti@unicatt.it   
Principal Investigator: Sergio Storti, MD         
Osp. civile di Carrara - Oncologia Medica Not yet recruiting
Carrara, Italy
Contact: Roberta Della Seta, MD       rdellaseta@alice.it   
Principal Investigator: Roberta Della Seta, MD         
Ospedale di Castelfranco Veneto - Ematologia Not yet recruiting
Castelfranco Veneto, Italy
Contact: Roberto Sartori, MD       roberto.sartori@aulss2.veneto.it   
Principal Investigator: Roberto Sartori, MD         
Arnas Nuovo Ospedale Garibaldi Nesima - U.O.C. Ematologia Not yet recruiting
Catania, Italy
Contact: Ugo Consoli, MD       ugo.consoli@tin.it   
Principal Investigator: Ugo Consoli, MD         
AO S.Antonio Abate - Oncologia Not yet recruiting
Gallarate, Italy
Contact: Fabrizio Ciambelli, MD       ciambelli@libero.it   
Principal Investigator: Fabrizio Ciambelli, MD         
Ospedali Riuniti del Canavese - S.C.Medicina trasfusionale ed Ematologia Not yet recruiting
Ivrea, Italy
Contact: Roberto Freilone, MD       rfreilone@aslto4.piemonte.it   
Principal Investigator: Roberto Freilone, MD         
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia Recruiting
Meldola, Italy
Contact: Gerardo Musuraca, MD       g.musuraca@irst.emr.it   
Principal Investigator: Gerardo Musuraca, MD         
Ospedale Dell'Angelo - U.O. Ematologia Not yet recruiting
Mestre, Italy
Contact: Renato Bassan, MD       renato.bassan@aulss3.veneto.it   
Principal Investigator: Renato Bassan, MD         
ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia Not yet recruiting
Milano, Italy
Contact: Vittorio Ruggero Zilioli, MD       vittorioruggero.zilioli@ospedaleniguarda.it   
Principal Investigator: Vittorio Ruggero Zilioli, MD         
P.O. San Martino - Ematologia Not yet recruiting
Oristano, Italy
Contact: Paolo Casula, MD       paolo.casula@asloristano.it   
Principal Investigator: Paolo Casula, MD         
AOU di Parma - UO Ematologia e CTMO Not yet recruiting
Parma, Italy
Contact: Francesca Re, MD       fre@ao.pr.it   
Principal Investigator: Francesca Re, MD         
Ospedale Guglielmo da Saliceto - U.O.Ematologia Not yet recruiting
Piacenza, Italy
Contact: Annalisa Arcari, MD       a.arcari@ausl.pc.it   
Principal Investigator: Annalisa Arcari, MD         
A.O.R. "San Carlo" - U.O. Ematologia Not yet recruiting
Potenza, Italy
Contact: Michele Cimminiello, MD       miki-doc@virgilio.it   
Principal Investigator: Michele Cimminiello, MD         
Ospedale delle Croci - Ematologia Not yet recruiting
Ravenna, Italy
Contact: Monica Tani, MD       monica.tani@auslromagna.it   
Principal Investigator: Monica Tani, MD         
A.O. Bianchi Melacrino Morelli - Ematologia Not yet recruiting
Reggio Calabria, Italy
Contact: Caterina Stelitano, MD       caterinastelitano27@gmail.com   
Principal Investigator: Caterina Stelitano, MD         
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS c/o CORE (II piano) - Ematologia Recruiting
Reggio Emilia, Italy
Contact: Francesco Merli, MD       merli.francesco@asmn.re.it   
Principal Investigator: Francesco Merli, MD         
Ospedale degli Infermi di Rimini - U.O. di Ematologia Not yet recruiting
Rimini, Italy
Contact: Anna Lia Molinari, MD       annalia.molinari@auslromagna.it   
Principal Investigator: Anna Lia Molinari, MD         
AO Sant'Andrea - Ematologia Recruiting
Roma, Italy
Contact: Maria Christina Cox, MD       chrisscox@gmail.com   
Principal Investigator: Maria Christina Cox, MD         
Ospedale S. Camillo - Ematologia Not yet recruiting
Roma, Italy
Contact: Roberta Battistini, MD       rbattistini@scamilloforlanini.rm.it   
Principal Investigator: Roberta Battistini, MD         
Policlinico Tor Vergata - Ematologia Not yet recruiting
Roma, Italy
Contact: Maria Cantonetti, MD       cantonetti@med.uniroma2.it   
Principal Investigator: Maria Cantonetti, MD         
Università Cattolica S. Cuore - Ematologia Not yet recruiting
Roma, Italy
Contact: Stefan Hohaus, MD       stefan.hohaus@Unicatt.it   
Principal Investigator: Stefan Hohaus, MD         
Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico Recruiting
Sassuolo, Italy
Contact: Giovanni Partesotti, MD       g.partesotti@ospedalesassuolo.it   
Principal Investigator: Giovanni Partesotti, MD         
AOU Senese - U.O.C. Ematologia Not yet recruiting
Siena, Italy
Contact: Alberto Fabbri, MD       a.fabbri@ao-siena.toscana.it   
Principal Investigator: Alberto Fabbri, MD         
Azienda Ospedaliera della Valtellina e della Valchiavenna P.O. Sondrio - Medicina Interna - Centro Malattie del Sangue P.O. Sondrio Not yet recruiting
Sondrio, Italy
Contact: Roberto Palazzolo, MD       roberto.palazzolo@asst-val.it   
Principal Investigator: Roberto Palazzolo, MD         
Ospedale SS. Annunziata ASL1 Abruzzo - U.O.S. Ematologia Universitaria Not yet recruiting
Sulmona, Italy
Contact: Sara Plebani, MD       plebani.sara@yahoo.it   
Principal Investigator: Sara Plebani, MD         
A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria Not yet recruiting
Torino, Italy
Contact: Federica Cavallo, MD       f.cavallo@unito.it   
Principal Investigator: Federica Cavallo, MD         
AO Ordine Mauriziano - SCDU Ematologia e Terapie Cellulari Not yet recruiting
Torino, Italy
Contact: Guido Parvis, MD       gparvis@mauriziano.it   
Principal Investigator: Guido Parvis, MD         
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Investigators
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Principal Investigator: Maria Christina Cox, MD Dpt of Oncology, Sant'Andrea Hospital, Via di Grottarossa, 00189 Roma, Italy

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Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT03161054     History of Changes
Other Study ID Numbers: FIL_DEVEC
First Posted: May 19, 2017    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione Italiana Linfomi ONLUS:
Metronomic Chemotherapy
Elderly non-fit patients
Aggressive B-Cell lymphomas
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Aggression
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Behavioral Symptoms
Prednisone
Cyclophosphamide
Rituximab
Etoposide
Etoposide phosphate
Vinorelbine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Anti-Inflammatory Agents
Glucocorticoids
Hormones