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

NCT01523834 | Completed Phase 2 Results DMC

• 2 other identifiers: FIL_PanAL102011-000175-13
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 10

Brief 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). 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).

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Diffuse Large B-cell Lymphoma (DLBCL); Panobinostat; Patients with relapsed/refractory DLBCL.

Outcome Measures

Primary Outcomes (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

  6 months

Secondary Outcomes (4)

• Complete Response (CR) Rate

  6 months

• Time to Response (TTR)

  36 months

• Progression Free Survival (PFS)

  36 months

• Overall Survival (OS)

  36 months

Study Arms (1)

Panobinosat

EXPERIMENTAL

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). 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.

Drug: Panobinostat

Interventions

Panobinostat DRUG

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.

Also known as: LBH589

Panobinosat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)
• 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)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (10)

Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo

Alessandria, 15121, Italy

Location

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

Bologna, 40138, Italy

Location

Spedali Civili

Brescia, Italy

Location

Ematologia I, A.O.U. San Martino

Genova, 16132, Italy

Location

Ospedale Umberto I - DH Oncoematologico

Nocera Inferiore, Italy

Location

Divisione di Ematologia Università Avogadro

Novara, Italy

Location

AO Ospedali Riuniti Villa Sofia-Cervello

Palermo, 90146, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

AO Universitaria di Udine

Udine, Italy

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Francesco Zaja, Co-Investigator of the Study
• Organization: Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica

francesco.zaja@asuiud.sanita.fvg.it

+39 0432559604

Study Officials

• Alessandro Levis, MD

  Fondazione Italiana Linfomi - ETS

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: February 1, 2012
• Study Start: February 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: April 1, 2017
• Last Updated: November 22, 2019
• Results First Posted: November 22, 2019

Record last verified: 2019-11

Locations

IT (10)