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

NCT ID: NCT03161054

Last Updated: 2021-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-12

Study Completion Date

2021-06-21

Brief Summary

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

Detailed Description

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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.

In Unfit and Frail patients with hemoglobin level at study entry \<11 gr/dL, will start etoposide will be orally administered at reduced dose (50 mg/day from day 1 to day 7). If hemoglobin will raise to ≥11 gr/dL, at subsequent induction cycles etoposide will be administered at full dose (50 mg/day, from day 1 to day 14), As a preventive measure, to avoid perforation, patients with gastrointestinal visceral involvement will receive a pre-phase therapy with steroids (prednisolone 40mg/m2

) for 6-7 days before starting protocol treatment. Moreover, in these patients the four Rituximab doses will be administered in cycle 2.

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.

Conditions

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Aggressive Non-Hodgkin Lymphoma

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

phase II, multicentre, non-randomized study, single arm study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Prednisone

Intervention Type 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).

Vinorelbine

Intervention Type 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).

Etoposide

Intervention Type 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

Cyclophosphamide

Intervention Type 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).

Rituximab

Intervention Type 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.

Interventions

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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).

Intervention Type 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).

Intervention Type 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

Intervention Type 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).

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francesco Merli, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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A.O. Spedali Civili di Brescia - Ematologia

Brescia, , Italy

Site Status

Ospedale di Castelfranco Veneto - Ematologia

Castelfranco Veneto, , Italy

Site Status

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

Meldola, , Italy

Site Status

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, , Italy

Site Status

Ospedale delle Croci - Ematologia

Ravenna, , Italy

Site Status

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

Reggio Emilia, , Italy

Site Status

AO Sant'Andrea - Ematologia

Roma, , Italy

Site Status

Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

Sassuolo, , Italy

Site Status

AOU Senese - U.O.C. Ematologia

Siena, , Italy

Site Status

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

Torino, , Italy

Site Status

Countries

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Italy

Other Identifiers

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FIL_DEVEC

Identifier Type: -

Identifier Source: org_study_id