Oral Panobinostat Adult Patients DLBCL Relapsed/Refractory Stem Cell Transfusion (ASCT) or Not Eligible for ASCT (FIL_PanAL10)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Fondazione Italiana Linfomi ONLUS.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier:
NCT01523834
First received: June 22, 2011
Last updated: January 30, 2012
Last verified: August 2011
  Purpose

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.

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).


Condition Intervention Phase
Diffuse Large B-cell Lymphoma
Drug: Panobinostat
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fondazione Italiana Linfomi ONLUS:

Primary Outcome Measures:
  • Overall response rate (ORR) at the end of the induction phase [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of patients achieving a Complete Response (CR) or Partial Response (PR) according to the Cheson 2007 response criteria


Secondary Outcome Measures:
  • Complete Response (CR) Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Proportion of CR at the end of the induction phase according to the Cheson 2007 response criteria

  • Time to response (TTR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    TTR is defined as the time from enrolment to Overall Response

  • Progression Free Survival (PFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from enrolment to disease progression or relapse or death from any cause

  • Overall toxicity measured by CTCAE v.4 [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    Proportion of Grade 3 or 4 non-hematologic toxicity

  • Overall Survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    OS is defined as the time from enrolment to death from any case


Estimated Enrollment: 35
Study Start Date: February 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Panobinostat

    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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient age is ≥ 18 years
  2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  3. Patient has a history of DLBCL according to the WHO classification
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
  10. Written informed consent was obtained from the patient prior to any study-specific screening procedures
  11. Patient has the ability to swallow capsules or tablets
  12. Practice acceptable birth control.

Exclusion Criteria:

  1. Patient has a history of prior treatment with a DAC inhibitors including panobinostat
  2. Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment
  3. 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
  4. Patient has been treated with any other anti lymphoma therapy within 3 weeks of start of study treatment
  5. Patient is using any anti-cancer therapy concomitantly
  6. Patient has been treated with > 5 prior systemic lines of treatment
  7. Patient has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment
  8. 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
  9. 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
  10. Patient has a history of CNS involvement with lymphoma
  11. 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)
  12. Patient has any other clinically significant heart disease (e.g., uncontrolled hypertension)
  13. 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)
  14. Patient has unresolved diarrhoea ≥ grade 2
  15. 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
  16. Patient has a known history of HIV seropositivity
  17. 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 +
  18. 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)
  19. 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
  20. 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
  21. 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
  22. 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01523834

Locations
Italy
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo Recruiting
Alessandria, Italy, 15121
Contact: Valentina Lenti, PhD    0131/206132    vlenti@ospedale.al.it   
Contact: Sonia Perticone, PhD    0131/206071    sperticone@ospedale.al.it   
Principal Investigator: Alessandro Levis, MD         
Centro di riferimento Oncologico Oncologia Medica A Not yet recruiting
Aviano (Pordenone), Italy
Contact: Michele Spina, MD    +39 0434/659730      
Principal Investigator: Michele Spina, MD         
Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola Active, not recruiting
Bologna, Italy, 40138
Divisione di Ematologia e TMO, Ospedale di Bolzano Not yet recruiting
Bolzano, Italy, 39100
Contact: Sergio Cortellazzo, MD    +39 0471 - 908807      
Principal Investigator: Sergio Cortelazzo, MD         
Spedali Civili Not yet recruiting
Brescia, Italy
Contact: Alessandra Tucci, MD    +39 030/3996269      
Principal Investigator: Alessandra Tucci, MD         
Ematologia I, A.O.U. San Martino Not yet recruiting
Genova, Italy, 16132
Contact: Angelo M Carella, Prof.    +39 010/513731      
Principal Investigator: Angelo M Carella, Prof.         
Ospedale S. Gerardo Divisione di ematologia Not yet recruiting
Monza (MI), Italy
Contact: Enrico Pogliani, Prof.    +39 039/2333435      
Principal Investigator: Enrico Pogliani, Prof.         
Ospedale Umberto I - DH Oncoematologico Not yet recruiting
Nocera Inferiore, Italy
Contact: Alfonso D'Arco, MD    +39 081/9213370      
Principal Investigator: Alfondo D'Arco, MD         
Divisione di Ematologia Università Avogadro Not yet recruiting
Novara, Italy
Contact: Gianluca Gaidano, Prof.    +39 0321/660663      
Principal Investigator: Gianluca Gaidano, MD         
Fondazione Policlinico San Matteo Clinica Ematologica Not yet recruiting
Pavia, Italy
Contact: Ercole Brusamolino, MD    +39 0382 503457      
Principal Investigator: Ercole Brusamolino, MD         
Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I - La Sapienza Active, not recruiting
Roma, Italy
Casa sollievo della sofferenza Not yet recruiting
San Giovanni Rotondo, Italy
Contact: Nicola Cascavilla, MD    +39 0882/410999      
Principal Investigator: Nicola Cascavilla, MD         
San Giovanni Battista Molinette - Biologia Molecolare Active, not recruiting
Torino, Italy
Ospedale San Giovanni Battista - Molinette Active, not recruiting
Torino, Italy
Osp. Cardinale Panico Divisione di Ematologia Not yet recruiting
Tricase (LE), Italy
Contact: Vincenzo Pavone, MD    +39 0833/773111      
Principal Investigator: Vincenzo Pavone, MD         
AO Universitaria di Udine Recruiting
Udine, Italy
Contact: Francesco Zaja, MD    +30 0432 559 620      
Principal Investigator: Francesco Zaja, MD         
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
  More Information

No publications provided

Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT01523834     History of Changes
Other Study ID Numbers: FIL_PanAL10, 2011-000175-13
Study First Received: June 22, 2011
Last Updated: January 30, 2012
Health Authority: Italy: The Italian Medicines Agency
Italy: Ministry of Health

Keywords provided by Fondazione Italiana Linfomi ONLUS:
Diffuse Large B-cell Lymphoma (DLBCL)
Panobinostat
Patients with relapsed/refractory DLBCL.

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Panobinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014