AzTrials
AzTrials

Diffuse Large B-cell Lymphoma RefractoryPhase 2/3FIL_VERAL12NCT01805557

Phase II Randomized Study With R-DHAP +/- Bortezomib as Induction Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Patients Eligible to Transplantation. BR-DHAP Versus R-DHAP.

A Phase 2/3 study testing R-DHAP and BR-DHAP in people with Diffuse Large B-cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by Fondazione Italiana Linfomi - ETS at 24 sites in Italy.

Completed

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

Official record
Search all trials

Trial summary

The probability to achieve CR with R-chemotherapy in patients failing a rituximab containing first line regimen is quite low, in particular in cases with non GCB profile. The bioCORAL trial suggest that ABC subset have a dismal outcome whichever the induction treatment. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
R-DHAP and BR-DHAP
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
24 sitesItaly
Study dates
4 Feb 2013to 20 Nov 2020
Phase
Phase 2/3
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18-65
  • Relapsed/refractory disease after receiving one line of standard chemoimmunotherapy (R-CHOP, GA-CHOP, R-CHOP like)
  • Diffuse Large B-cell Lymphoma at relapse. Patient has to be re-biopsied prior to study entry. If this is harmful for the patient, the patient can be enrolled if archivial tumor sample and block from first diagnosis are available.
  • No prior Bortezomib therapy
  • Measurable and/or evaluable disease
  • Any Ann Arbor stage and IPI group at relapse
Show all 28Show fewer
  • Performance status < 2 according to ECOG scale unless due to lymphoma
  • No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
  • Adequate hematological counts: ANC > 1.5 x 109/L, Hgb > 9 g/dl (transfusion independent), Platelet count > 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement
  • HIV negativity, HCV negativity, HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)
  • Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total < 2 x ULN) if not related to lymphoma
  • Normal kidney function (creatinine clearance > 45 ml/min)
  • Cardiac ejection fraction > 50% (MUGA scan or echocardiography)
  • Normal lung function
  • Absence of active opportunistic infections
  • Non peripheral neuropathy or active neurological non neoplastic disease of CNS
  • Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or no other disease life-threatening that can compromise chemotherapy treatment
  • Disease free of prior malignancies other than lymphoma for > 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
  • Life expectancy > 6 months
  • No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
  • Written informed consent
  • Women must be:
  • postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
  • surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
  • abstinent (at the discretion of the investigator/per local regulations), or
  • if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 12 months after terminating treatment.
  • Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening
  • Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.

Who cannot join

  • Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma g I-II-IIIa-IIIb, Primary Mediastinal Lymphoma
  • Age > 65 years
  • Patients ineligible to high-dose chemotherapy
  • Performance status > 2 according to ECOG scale if not due to lymphoma
  • Patient has known or suspected hypersensitivity or intolerance to Rituximab
  • Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
Show all 20Show fewer
  • CNS disease (meningeal and/or brain involvement by lymphoma)
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
  • Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
  • Cardiac ejection fraction < 50% (MUGA scan or echocardiography)
  • Creatinine clearance < 45 ml/min
  • Presence of major neurological disorders
  • HIV positivity, HCV positivity, HBV positivity with the exception of patients with HBcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
  • Active opportunistic infection
  • Major surgical intervention prior 3 months to randomization if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
  • Prior malignancies other than lymphoma in the last 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
  • Life expectancy < 6 months
  • Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
  • If female, the patient is pregnant or breast-feeding.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

Italy24 sites

  • A.O. SS. Antonio e Biagio e C. Arrigo

    Alessandria, 15121

  • Clinica di ematologia AOU Umberto I Ospedali Riuniti

    Ancona, 60100

  • CRO Aviano

    Aviano, Pordenone, 33081

  • ASST Spedali Civili di Brescia - Ematologia

    Brescia, 25123

  • Ospedale Businco - SC Ematologia e CTMO

    Cagliari, 09121

  • ASST Valle Olona

    Gallarate, Varese

  • Ematologia 1 Ospedale S. Martino

    Genova, 16132

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Ematologia

    Meldola, Forlì-Cesena, 47014

  • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

    Milan, MI, 20162

  • SC Ematologia - Trapianto di midollo osseo Fond. IRCCS Istituto Nazionale Tumori

    Milan, 20133

  • SCDU Ematologia - Università del Piemonte Orientale

    Novara, 28100

  • Ospedale S. Antonio

    Padova, 35128

  • U.O. Complessa di Ematologia Ospedale di Parma

    Parma, 43100

  • Ospedale Civile Guglielmo da Saliceto

    Piacenza, 29121

  • Osp. S. Maria delle Croci

    Ravenna, 48121

  • Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Ematologia

    Reggio Calabria, 89124

  • AO Arcispedale S.Maria Nuova Ematologia

    Reggio Emilia, 42123

  • Osp. degli Infermi Divisione di Oncologia

    Rimini, 47923

  • A.O. Universitaria S. Andrea

    Roma, 00189

  • Clinica Humanitas

    Rozzano, Milano, 20089

  • SC Oncoematologia con autotrapianto AO Santa Maria

    Terni, 05100

  • AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria

    Torino, 10126

  • AOU Citta della Salute e della Scienza di Torino-SC Ematologia

    Torino, 10126

  • Azienda Ospedaliero - Universitaria di Udine

    Udine, 33100

Other trials in Italy

About this study

The probability to achieve CR with R-chemotherapy in patients failing a rituximab containing first line regimen is quite low, in particular in cases with non GCB profile. The bioCORAL trial suggest that ABC subset have a dismal outcome whichever the induction treatment. Thus it can be argued the addition of new molecule to the RDHAP regimen could be of value. Bortezomib appears the best candidate in this setting as ABC subtypes constitutively express NFkb, which is the target of bortezomib itself. Data from the literature suggest an encouraging activity of R-chemo+ bortezomib in non GCB-derived DLBCL, although in small series. Thus, the addition of bortezomib is here justified by the need to circumvent constitutional resistance to chemotherapy. Published experience of the association between bortezomib and cytarabine are also encouraging with acceptable cumulative toxicity.

Read the detailed description

This is a prospective, multicenter, two-arm randomized phase II screening trial34 in young patients (18-65 years) affected by relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) at diagnosis, eligible to high-dose therapy.

Aim of the study is to to assess whether the addition of Bortezomib to R-DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy with ASCT with respect to response and safety. Patients will be randomized at first relapse between: a) the standard salvage therapy Rituximab in association to DHAP every 28 days (R-DHAP) for 4 cycles and b) Bortezomib in association to the same regimen (BR-DHAP). In both arms the induction therapy is followed by autologous stem cell transplantation or, if indicated, by allogeneic stem cell transplant.

A patient is considered evaluable if it is possible to assess response by PET after 4 cycle or, if a patient withdraws from the study for PD, before completion of study treatment.

After providing written informed consent, patients will be evaluated for eligibility during a 21-day screening period. If they continue to meet eligibility criteria, they will be randomized to receive the first dose of BR-DHAP or R-DHAP .

Being tested
R-DHAP, BR-DHAP
Keywords
Diffuse Large B-cell Lymphoma (DLBCL), Bortezomib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • R-DHAPDrug

    • Rituximab 375 mg/sqm iv day 0 or 1
    • Cisplatin 100 mg/sqm iv day 1 in 6-hours infusion
    • Cytarabine 2000 mg/sqm in 3-hours infusion iv day 2 and day 3
    • Dexamethasone 40 mg day 1-4
    • Pegfilgrastim 6 mg sc monodose 24 hours after the end of chemotherapy or G-CSF from day 5 till stem cell harvest during mobilization's course (II o III cycle R-DHAP)
    • Rituximab 375 mg/sqm iv 24 hours before apheresis as purging in vivo during second courses of therapy

  • BR-DHAPDrug

    • Rituximab 375 mg/sqm iv day 0 or 1
    • Bortezomib SC 1.5 mg/sqm day 1, day 4
    • Cisplatin 100 mg/sqm iv day 1 in 6-hours infusion
    • Cytarabine 2000 mg/sqm in 3-hours infusion iv day 2 and day 3
    • Dexamethasone 40 mg day 1-4
    • Pegfilgrastim 6 mg sc monodose 24 hours after the end of chemotherapy or G-CSF from day 5 till stem cell harvest during mobilization's course (II o III cycle R-DHAP)
    • Rituximab 375 mg/sqm iv 24 hours before apheresis as purging in vivo during second courses of therapy Chemotherapy R-DHAP and BR-DHAP will be repeated every 28 days.
Study groups in NCT01805557
Study groupRoleWhat they receive
R-DHAPActive comparatorR-DHAP x 2, restaging, mobilization and harvest of peripheral stem cell + R-DHAP x 2, restaging with PET evaluation
Receives: Drug: R-DHAP
BR-DHAPExperimentalBortezomib + R-DHAP x 2, restaging, mobilization and harvest of peripheral stem cell + Bortezomib + R-DHAP x 2, restaging with PET evaluation
Receives: Drug: R-DHAP; Drug: BR-DHAP

What is being measured

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

  1. Complete Response (CR) Rate

    Proportion of CR according to the Cheson 2007 response criteria, evaluated by PET scan

    Measured: At the end of the induction phase (6 months)

Secondary outcomes (5)

  1. Overall Response Rate (ORR)

    ORR at the end of the induction treatment is defined as Complete Response (CR) or Partial Response according to the Cheson 2007 response criteria, evaluated by PET scan

    Measured: At the end of the induction phase (6 months)

  2. Overall Survival (OS)

    OS will be defined as the time between the date of randomization and the date of death from any cause

    Measured: 36 months

  3. Number of Patients With Treatment-Related Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety

    Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during therapy

    Measured: 12 months

  4. Mobilizing potential

    Amount of CD34+ stem cell collected/Kg

    Measured: 6 months

  5. Number of Patients completing ASCT

    Proportion of randomized patients successfully completing ASCT

    Measured: 12 months

Timeline

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

  1. First posted6 Mar 2013 (estimated)
  2. Study start4 Feb 2013
  3. Primary completion12 Mar 2019
  4. Study completion20 Nov 2020

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01805557
Sponsor's protocol ID
FIL_VERAL12
Acronym
FIL_VERAL12
Status last verified
Jun 2022
First submitted
5 Mar 2013
Last updated
8 Jun 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing R-DHAP and BR-DHAP in people with Diffuse Large B-cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by Fondazione Italiana Linfomi - ETS at 24 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 28 inclusion and 20 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 8 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Response (CR) Rate (time frame: At the end of the induction phase (6 months)). 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 NCT01805557.

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 8 Jun 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in