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Aggressive Non-Hodgkin LymphomaPhase 2NCT03161054

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

A Phase 2 study testing Prednisone, Vinorelbine and Etoposide in people with Aggressive Non-Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 10 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 65 years and older
Conditions the study is for
Aggressive Non-Hodgkin Lymphoma
What is being tested?
Prednisone, Vinorelbine and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
10 sitesItaly
Study dates
12 Sep 2017to 21 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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;
Show all 23Show fewer
  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Italy10 sites

  • A.O. Spedali Civili di Brescia - Ematologia

    Brescia

  • Ospedale di Castelfranco Veneto - Ematologia

    Castelfranco Veneto

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

    Meldola

  • Ospedale Guglielmo da Saliceto - U.O.Ematologia

    Piacenza

  • Ospedale delle Croci - Ematologia

    Ravenna

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

    Reggio Emilia

  • AO Sant'Andrea - Ematologia

    Roma

  • Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

    Sassuolo

  • AOU Senese - U.O.C. Ematologia

    Siena

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

    Torino

Other trials in Italy

About this study

Official title: A Phase II Study of Metronomic Chemotherapy in Elderly Non-fit Patients (>65 Years) With Aggressive B-Cell Lymphomas

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

Read the 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.

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.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrednisoneDrug

    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).

  • VinorelbineDrug

    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).

  • EtoposideDrug

    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

  • CyclophosphamideDrug

    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).

  • RituximabDrug

    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.

Study groups in NCT03161054
Study groupRoleWhat they receive
One arm for all patientExperimentalInduction 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
Receives: Drug: Prednisone; Drug: Vinorelbine; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 30 months

  2. 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

    Measured: 30 months

Secondary outcomes (7)

  1. Overall response rate (ORR)

    ORR, defined as the proportion of patients who achieved a CR (including CRu) or a PR.

    Measured: 30 months

  2. Clinical Benefit

    Defined as the percentage of patients who achieved a CR (including CRu), a PR and a SD.

    Measured: 30 months

  3. Progression Free Survival (PFS)

    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.

    Measured: 36

  4. Event Free Survival (EFS)

    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.

    Measured: 36

  5. Disease Free Survival (DFS)

    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.

    Measured: 36

  6. Overall Survival (OS)

    OS, calculated from the date of registration until death for any cause or last follow-up in censored patients.

    Measured: 36

  7. Patient-Reported Outcome (PRO)

    PRO per European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QLQ-30) questionnaire

    Measured: 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start12 Sep 2017
  3. Primary completion22 Apr 2020
  4. Study completion21 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
phase II, multicentre, non-randomized study, single arm study
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03161054
Sponsor's protocol ID
FIL_DEVEC
Status last verified
Dec 2021
First submitted
18 May 2017
Last updated
20 Dec 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Prednisone, Vinorelbine and Etoposide in people with Aggressive Non-Hodgkin Lymphoma, run by Fondazione Italiana Linfomi - ETS at 10 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Remission Rate (CRR) (time frame: 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03161054.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2021.

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