AzTrials
AzTrials

Diffuse Large B-cell LymphomaPhase 2FIL_PanAL10NCT01523834

Oral Panobinostat Adult Patients DLBCL Relapsed/Refractory Stem Cell Transfusion (ASCT) or Not Eligible for ASCT

A Phase 2 study testing Panobinostat in people with Diffuse Large B-cell 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
Search all trials

Trial summary

Treatment of adult patients with Diffuse Large B-cell Lymphoma (DLBCL), relapsed or refractory to previous CHOP-R (or CHOP-R like regimen) front line therapy, relapsed or refractory to second or subsequent salvage therapies which included high dose therapy with autologous stem cell support (ASCT). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Panobinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
10 sitesItaly
Study dates
Feb 2011to Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient age is ≥ 18 years
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Patient has a history of DLBCL according to the WHO classification
  • Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT
  • Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT
  • Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy
Show all 18Show fewer
  • Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement
  • Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail):
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L [SI units 1.5 x 109/L]
  • Platelet count ≥ 100 x 109/L
  • Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution
  • Serum creatinine ≤ 1.5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome)
  • AST/SGOT and/or ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
  • Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
  • Written informed consent was obtained from the patient prior to any study-specific screening procedures
  • Patient has the ability to swallow capsules or tablets
  • Practice acceptable birth control.

Who cannot join

  • Patient has a history of prior treatment with a DAC inhibitors including panobinostat
  • Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment
  • Patient has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment
  • Patient has been treated with any other anti lymphoma therapy within 3 weeks of start of study treatment
  • Patient is using any anti-cancer therapy concomitantly
  • Patient has been treated with > 5 prior systemic lines of treatment
Show all 29Show fewer
  • Patient has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment
  • Patient treated with allogeneic hematopoietic stem cell transplant with active progressive cGVHD; patient has received DLI ≤ 6 weeks prior to start of study treatment; patient is planned to receive DLI
  • Patient has a history of another malignancy ≤ 3 years before study entry, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix
  • Patient has a history of CNS involvement with lymphoma
  • Patient has impaired cardiac function including any of the following:
  • Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute), QTcF > 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
  • Presence of unstable atrial fibrillation (ventricular heart rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
  • Previous history angina pectoris or acute MI within 6 months
  • Congestive heart failure (New York Heart Association functional classification III-IV)
  • Patient has any other clinically significant heart disease (e.g., uncontrolled hypertension)
  • Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
  • Patient has unresolved diarrhoea ≥ grade 2
  • Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patient has a known history of HIV seropositivity
  • Patient has active HBV hepatitis. The following categories of patients HBV positive but with non evidence of active hepatitis may be considered for the study and treated with panobinostat (see also Section 8.12 of the study protocol):
  • patient is HBsAg + with HBV DNA < 2000 UI/ml (inactive carriers); HBV DNA > 2000 UI/ml is criteria of exclusion
  • patient is HBsAg - HBsAb +
  • patient is HBsAg - but HBcAb +
  • Patients with HCV active hepatitis are excluded from the study. Patient with no evidence of active hepatitis and/or advanced chronic liver disease according to liver biopsy or fibro-scan evaluation may be included into the study (see also Section 8.12 of the study protocol)
  • Patient is using medications that have a relative risk of prolonging the QT interval or of inducing "Torsade de Pointes", where such treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months or had menses any time in the preceding 12 consecutive months. WOCBP must have a negative serum pregnancy test at baseline
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use a double method of contraception, one of which includes a condom, during the study and for 3 months after the end of treatment
  • Patient does not have before entering into the study a new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Italy10 sites

  • Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo

    Alessandria, 15121

  • Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola

    Bologna, 40138

  • Spedali Civili

    Brescia

  • Ematologia I, A.O.U. San Martino

    Genova, 16132

  • Ospedale Umberto I - DH Oncoematologico

    Nocera Inferiore

  • Divisione di Ematologia Università Avogadro

    Novara

  • AO Ospedali Riuniti Villa Sofia-Cervello

    Palermo, 90146

  • A.O. Città della Salute e della Scienza (Ematologia Univ)

    Torino

  • A.O. Città della salute e della scienza (S.C. Ematologia)

    Torino

  • AO Universitaria di Udine

    Udine

Other trials in Italy

About this study

Official title: A Phase II Study of Oral Panobinostat in Adult Patients With Diffuse Large B-cell Lymphoma Relapsed/Refractory After High-dose Chemotherapy With Autologous Stem Cell Transfusion (ASCT) or Not Eligible for ASCT

Treatment of adult patients with Diffuse Large B-cell Lymphoma (DLBCL), relapsed or refractory to previous CHOP-R (or CHOP-R like regimen) front line therapy, relapsed or refractory to second or subsequent salvage therapies which included high dose therapy with autologous stem cell support (ASCT).

Treatment of adult patients with DLBCL relapsed or refractory to front line therapy with CHOP-R (or CHOP-R like regimen) or subsequent treatments, who are not consider eligible for ASCT consolidation because of age, co-morbidities, impossibility to perform ASCT.

Read more

The trial is conducted according to the optimal two-stage design of Simon with alpha 0.05 and beta 0.10, considering the following two hypotheses: first a response rate (RR) less than 10% is of no further interest; and second, an RR 30% is clinically meaningful. In the initial stage, 18 patients have to enter onto the study. If less than 3 responses (</=2 in 18) will be observed, the trial would be terminated. Otherwise, accrual will continue to a total of a maximum of 35 patients. At the end of the trial, if 6 or fewer responses will occur among the 35 patients (</= 6 in 35), it will be concluded that the regimen is not worthy of further investigations for that group of patients.

The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason).

Read the detailed description

Overview Of Study Design This is a prospective, multicenter phase II trial designed to evaluate the safety and activity of the panobinostat in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Study design The trial is conducted according to the optimal two-stage design of Simon with alpha 0.05 and beta 0.10, considering the following two hypotheses: first a response rate (RR) less than 10% is of no further interest; and second, an RR 30% is clinically meaningful. In the initial stage, 18 patients have to enter onto the study. If less than 3 responses (£ 2 in 18) will be observed, the trial would be terminated. Otherwise, accrual will continue to a total of a maximum of 35 patients. At the end of the trial, if 6 or fewer responses will occur among the 35 patients (£ 6 in 35), it will be concluded that the regimen is not worthy of further investigations for that group of patients. The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). Study duration This study is expected to start in February 2011. The last patient is expected to be enrolled at the end of January 2013. Considering a possible treatment duration of 24 months, this trial is due to be completed by January 2015.

Objectives:

Primary objective 1. To explore the antitumor activity of panobinostat in term of overall response (OR) at the end of the induction phase (i.e. month 6 from the beginning of panobinostat) Secondary objectives

  1. To explore the antitumor activity of panobinostat in terms of Complete Response (CR)
  2. To assess the time to response (TTR)
  3. To evaluate Progression Free Survival (PFS)
  4. To assess the safety and tolerability of panobinostat
  5. To evaluate the Overall Survival (OS) Exploratory objectives
  6. To study the impact of pharmacogenetics in predicting the response to panobinostat 2. To study the impact of immunohistochemical patterns and patient's specific gene expression and response to panobinostat 3. To assess the correlation between "telomeric asset" and response to panobinostat
Being tested
Panobinostat
Keywords
Diffuse Large B-cell Lymphoma (DLBCL), Panobinostat, Patients with relapsed/refractory DLBCL.
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.

  • PanobinostatDrug

    Also called LBH589

    Induction Phase: Patients will receive panobinostat for 6 courses (1 course = 28 days). Consolidation phase (courses 7-12). Maintenance phase (course 13-end of therapy).

    Panobinostat should be taken p.o. at the dose of 40 mg/day 3-times every week (QW) as part of a 4 week treatment cycle. The dose of panobinostat may be modified: the 1st dose adjustment consists in the modification of drug administration from 3 times every week (QW) to 3 times every other week (QOW). Levels lower than 30 mg 3 times QOW is not permitted.

Study groups in NCT01523834
Study groupRoleWhat they receive
PanobinosatExperimentalThe treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). The duration of a treatment course will be 28 days. The first dose of panobinostat in course 1 defines day 1 of the treatment cycle, and each cycle thereafter will begin 28 days later. Treatment: Panobinostat should be taken p.o. at the dose of 40 mg/day three-times every week (QW) (e.g., on Monday, Wednesday, and Friday or Tuesday, Thursday, and Saturday), as part of a 4 week (28 days) treatment cycle.
Receives: Drug: Panobinostat

What is being measured

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

  1. Overall Response Rate (ORR) at the End of the Induction Phase

    ORR is defined as the proportion of patients achieving a Complete Response (CR) or Partial Response (PR) according to the Cheson 1999 response criteria

    Measured: 6 months

Secondary outcomes (4)

  1. Complete Response (CR) Rate

    Proportion of CR at the end of the induction phase according to the Cheson 1999 response criteria

    Measured: 6 months

  2. Time to Response (TTR)

    TTR is defined as the time from enrolment to Overall Response

    Measured: 36 months

  3. Progression Free Survival (PFS)

    PFS is defined as the time from enrolment to disease progression or relapse or death from any cause

    Measured: 36 months

  4. Overall Survival (OS)

    OS is defined as the time from enrolment to death from any case

    Measured: 36 months

Timeline

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

  1. First posted1 Feb 2012 (estimated)
  2. Study startFeb 2011
  3. Primary completionJan 2014
  4. Study completionApr 2017

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
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01523834
Sponsor's protocol ID
FIL_PanAL10
Other IDs
2011-000175-13
Acronym
FIL_PanAL10
Status last verified
Nov 2019
First submitted
22 Jun 2011
Last updated
22 Nov 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panobinostat in people with Diffuse Large B-cell 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 18 inclusion and 29 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 22 Nov 2019. 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?

Yes. Results are posted in the registry (first posted 22 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (ORR) at the End of the Induction Phase (time frame: 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 NCT01523834.

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 22 Nov 2019.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in