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

NCT01238692 | Completed Phase 2 DMC

• 1 other identifier: Q-CROC-02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse large B cell lymphoma; DLBCL; Relapsed B-cell lymphoma; Refractory B-cell lymphoma; B-cell Lymphoma; Panobinostat; LBH589; Rituximab; Histone Deacetylase Inhibitors

Outcome Measures

Primary Outcomes (1)

• Efficacy of LBH589 alone and when given in combination with rituximab

  2 years

Secondary Outcomes (2)

• Safety and tolerability of single agent LBH589 therapy and combination therapy of LBH589 with rituximab

  2 years

• Identify potential biological factors that might correlate with efficacy

  2 years

Study Arms (2)

LBH589

EXPERIMENTAL

Drug: LBH589

LBH589 plus Rituximab

EXPERIMENTAL

Drug: LBH589; Drug: Rituximab

Interventions

LBH589 DRUG

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.

Also known as: Panabinostat

LBH589; LBH589 plus Rituximab

Rituximab DRUG

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 The appropriate amount of solution should be withdrawn from the vial for the following calculation: Volume (mL) = BSA (m2) × dose (375 mg/m2) / concentration of reconstituted solution ml/mL (100 mg/10 mL and/or 500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).

Also known as: MabThera IV

LBH589 plus Rituximab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sarit Assouline: lead
• Quebec Clinical Research Organization in Cancer: collaborator
• Novartis: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (4)

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, H3T 1E2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Sacré-Cœur Hospital

Montreal, Quebec, H4J 1C5, Canada

Location

Related Publications (1)

• Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. doi: 10.1182/blood-2016-02-699520. Epub 2016 May 10.

  PMID: 27166360 RESULT

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell

Interventions

Panobinostat; Rituximab

Condition Hierarchy (Ancestors)

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sarit Assouline, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician, Division of Hematology, Jewish General Hospital. Assistant Professor, Department of Oncology, McGill University

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 11, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

CA (4)