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A Phase II Study of Oral Panobinostat (LBH589) and Rituximab to Treat Diffuse Large B Cell Lymphoma (DLBCL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01238692
Recruitment Status : Active, not recruiting
First Posted : November 11, 2010
Last Update Posted : December 6, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of the study is to examine both efficacy of LBH589 in treating relapsed and refractory DLBCL, and added benefit of combining rituximab with LBH589 in this setting. Tissue samples from accessible lymph nodes will be collected and banked before the start of the study treatment and after 15 days. Additionally, blood samples will be drawn and stored in the tissue biobank.

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma Drug: LBH589 Drug: Rituximab Phase 2

Detailed Description:

This is a randomized Phase II, multi-center study of LBH589 given alone (Arm A) or in combination with rituximab (Arm B).

The objectives of this study are:

  • To investigate the efficacy of LBH589 alone and in addition to rituximab in patients with relapsed or refractory DLBCL.
  • To investigate the safety and tolerability of single agent LBH589 therapy and combination therapy of LBH589 with rituximab.
  • To identify potential biological factors that might correlate with efficacy.

LBH589 will be given at a dose of 30mg orally every Monday, Wednesday and Friday, as in other studies of this agent. Rituximab will be given as a single 375mg/m2 dose intravenously on day 1 of each cycle. Treatment may be administered up to 6 cycles. Treatment beyond 6 cycles will be discussed with the Sponsor. Each cycle will last 21 days.

A Phase I, dose-escalation component to the study, to determine the recommended phase II dose of rituximab in combination with LBH589, is not considered necessary as the respective toxicity profiles of these two drugs do not predict for overlapping toxicity. Dose de-escalation of LBH589 will be performed for toxicity. No dose escalations will be permitted. If patients experience grade 2 or more toxicity not returning to grade < 1 within 4 weeks after stopping therapy, they will not be allowed to continue on therapy. If more than two dose interruptions are required for toxicity, this will also be a reason to be removed from the study.

An interim analysis for safety and futility will be performed after a total of 10 patients in each arm have been enrolled.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Oral Panobinostat (LBH589) With or Without Rituximab to Treat Relapsed or Refractory Diffuse Large B Cell Lymphoma
Study Start Date : November 2010
Primary Completion Date : January 2016
Estimated Study Completion Date : December 2016

Arms and Interventions

Arm Intervention/treatment
Experimental: LBH589 Drug: LBH589
Patients randomized to both arms will receive oral LBH589, once-a-day, at a dose of 30 mg/day, on a three times-a-week (Monday, Wednesday and Friday) schedule as part of a 3 week (21 day) treatment cycle. Day one of each cycle will be on a Monday.
Other Name: Panabinostat
Experimental: LBH589 plus Rituximab Drug: LBH589
Patients randomized to both arms will receive oral LBH589, once-a-day, at a dose of 30 mg/day, on a three times-a-week (Monday, Wednesday and Friday) schedule as part of a 3 week (21 day) treatment cycle. Day one of each cycle will be on a Monday.
Other Name: Panabinostat
Drug: Rituximab

Patients randomized to Arm B will receive IV rituximab at a dose of 375 mg/m2 in combination with oral LBH589. Rituximab should be administered on the same day as LBH589, after the patient has taken their LBH589 dose. The appropriate amount of solution should be withdrawn from the vial for the following calculation:

Volume (mL) = BSA (m2) × dose (375 mg/m2) / concentration of reconstituted solution ml/mL (100 mg/10 mL and/or 500 mg/50 mL).

Other Name: MabThera IV

Outcome Measures

Primary Outcome Measures :
  1. Efficacy of LBH589 alone and when given in combination with rituximab [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Safety and tolerability of single agent LBH589 therapy and combination therapy of LBH589 with rituximab [ Time Frame: 2 years ]
  2. Identify potential biological factors that might correlate with efficacy [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pathological confirmation of any stage of DLBCL. Patients with transformation to DLBCL will be permitted on study.
  • Patients must have received at least 1 prior line of treatment if not eligible for an autologous stem cell transplant (ASCT) or 2 prior therapies, one of which must have been an ASCT, if eligible for such therapy.
  • Patients must have received prior rituximab therapy and the last treatment administered with rituximab must have been given at least 6 months prior to study registration on this trial. Exception may be granted to patients treated with rituximab or other anti-CD20 monoclonal antibody 3-6 months prior to study registration upon discussion with the Sponsor.
  • Patients must have at least one site of bi-dimensionally measurable lesion (> 1.5 cm in its largest dimension by CT scan).
  • ECOG performance status of 0 or 1.
  • Age 18 years or older.
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal (results 3 months prior to study registration is acceptable).
  • Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.

Exclusion Criteria:

  • Prior use of any anti-CD20 monoclonal antibody within 6 months of study start (refer to inclusion #3 for exception).
  • History of serious infusion-related reaction to rituximab or other monoclonal antibodies.
  • Central nervous system lymphoma.
  • Prior treatment with HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
  • Evidence of significant, uncontrolled concomitant disease which could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
  • Impaired cardiac function
  • Uncontrolled hypertension.
  • Concomitant use of CYP3A4/5 inhibitors.
  • Concomitant use of drugs with a risk of causing "torsades de pointes".
  • Patients with unresolved diarrhea ≥ CTCAE grade 1.
  • Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral LBH589.
  • Patients who have received treatment for DLBCL ≤ 3 weeks prior to starting the study treatment or who have not recovered from side effects of such therapy.
  • Women who are pregnant of breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier 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 (ie. who has had menses any time preceding 12 consecutive months). WOCBP must have a negative serum pregnancy test at baseline.
  • Male patients whose sexual partners are WOCBP not using double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
  • Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, completely excised melanoma-in-situ, or basal or squamous cell carcinoma of the skin.
  • Patients with a known positivity for HIV or hepatitis C; baseline testing for HIV and hepatitis C is not required.
  • Patients with hepatitis B sAg positivity will be excluded. However, exceptions may be granted but only after discussion between the Sponsor and the site. Patients with hepatitis B core antibody positivity only must also be discussed with the Sponsor prior to entry on study (results 6 months prior to study registration is acceptable).
  • Patients who cannot stop ingestion of grapefruits, starfruit, or Seville oranges
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01238692

Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, H3T 1E2
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T1E2
Sacré-Cœur Hospital
Montreal, Quebec, Canada, H4J 1C5
Sponsors and Collaborators
Sarit Assouline
Quebec Clinical Research Organization in Cancer
Hoffmann-La Roche
Principal Investigator: Sarit Assouline, MD Jewish General Hospital
More Information

Responsible Party: Sarit Assouline, Physician, Division of Hematology, Jewish General Hospital. Assistant Professor, Department of Oncology, McGill University, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT01238692     History of Changes
Other Study ID Numbers: Q-CROC-02
First Posted: November 11, 2010    Key Record Dates
Last Update Posted: December 6, 2016
Last Verified: December 2016

Keywords provided by Sarit Assouline, Jewish General Hospital:
Diffuse large B cell lymphoma
Relapsed B-cell lymphoma
Refractory B-cell lymphoma
B-cell Lymphoma
Histone Deacetylase Inhibitors

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Histone Deacetylase Inhibitors
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action