Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

NCT01261247 | Completed Phase 2 Results DMC

• 4 other identifiers: MC0986NCI-2010-0232610-004705CLBH589BUS59T
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well panobinostat works in treating patients with relapsed or refractory non-Hodgkin lymphoma

Conditions

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Confirmed Responses Defined to be a CR or PR Noted as the Objective Status

  The primary endpoint of this phase II trial is the proportion of confirmed responses (complete response (CR) or partial response (PR)) noted as the objective status and will be considered synonymous with "success" for this study.Response will be evaluated using all cycles of treatment. A CR is defined using the Cheson et al. Revised Response Criteria for Malignant Lymphoma as Disappearance of all evidence of disease. A PR is defined as Regression of measurable disease and no new sites with ≥50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients.

  Every 28 days for up to 2 years

Secondary Outcomes (3)

• Median Overall Survival Time

  Every 6 months for up to 2 years

• Median Progression-free Survival Time

  Every 6 months for up to 2 years

• Duration of Response

  Every 6 months for up to 2 years

Other Outcomes (1)

• Pharmacokinetic/Pharmacodynamic of LBH589 and Correlation With Clinical Effects as Assessed by Immunoblotting, SNPs Analysis, Serum Cytokine Assays, and Flow Cytometry for Suppressive Monocytes (Correlative Studies)

  At baseline and day 1 of courses 3, 5, 7 and every three courses thereafter for up to 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral panobinostat 3 times weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: panobinostat; Other: laboratory biomarker analysis; Genetic: western blotting; Genetic: DNA analysis; Other: flow cytometry; Other: pharmacological study; Other: immunohistochemistry staining method

Interventions

panobinostat DRUG

Given orally

Also known as: Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

western blotting GENETIC

Correlative studies

Also known as: Blotting, Western, Western Blot

Arm I

DNA analysis GENETIC

Correlative studies

Arm I

flow cytometry OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

immunohistochemistry staining method OTHER

Optional correlative studies

Also known as: immunohistochemistry

Arm I

Eligibility Criteria

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

You may qualify if:

• Biopsy-proven relapsed or refractory non-Hodgkin lymphoma requiring treatment, who have failed, unable to tolerate, or refused other available active therapies; patients should not have other treatment options considered curative (NOTE: for patients with lymphoma without CNS involvement, a re-biopsy is necessary unless the patient has had a previous biopsy =\< 6 months prior to treatment on this protocol if there has been no intervening treatment; patients with biopsy-proven CNS lymphoma at any time are not required to have a rebiopsy to be eligible for this study); NOTE: relapsed NHL is defined as NHL that relapses after at least one prior therapy and does not have available curative therapy; refractory NHL is defined as NHL that has progressed or not responded to most recent therapy and has had at least one prior therapy and have no available curative therapies
• Measurable disease by CT or MRI or the CT portion of the PET/CT: must have at least one lesion that has a single diameter of \>= 2 cm or tumor cells in the blood \>= 5 x 10\^9/L; skin lesions can be used if the area is \>= 2 cm in at least one diameter and photographed with a ruler
• The following disease types are eligible: transformed lymphomas: diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma grade III; precursor B lymphoblastic leukemia/lymphoma; mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma/leukemia; precursor T-lymphoblastic leukemia/lymphoma; primary cutaneous anaplastic large cell lymphoma; anaplastic large cell lymphoma - primary systemic type; small lymphocytic lymphoma/chronic lymphocytic leukemia; follicular lymphoma, grades 1, 2; extranodal marginal zone B-cell lymphoma of MALT type; nodal marginal zone B-cell lymphoma; splenic marginal zone B-cell lymphoma; peripheral T cell lymphoma, unspecified; anaplastic large cell lymphoma (T and null cell type); lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); CNS lymphoma; post transplant lymphoproliferative disorders; mycosis fungoides/Sezary syndrome; primary effusion lymphoma; blastic NK-cell lymphoma; adult T-cell leukemia/lymphoma; extranodal NK/T-cell lymphoma, nasal type; enteropathy-type T-cell lymphoma; hepatosplenic T-cell lymphoma; subcutaneous panniculitis-like T-cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma - primary cutaneous type
• For lymphoplasmacytic lymphoma patients without measurable lymphadenopathy, measurable disease can be defined by both of the following criteria: bone marrow lymphoplasmacytosis with \> 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy and quantitative IgM monoclonal protein \> 1,000 mg/dL
• ANC \>= 1000/uL
• Hgb \>= 9 g/dl
• PLT \>= 75,000/uL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) or if total bilirubin is \> 1.5 x ULN the direct bilirubin must be normal
• AST =\< 3 x ULN
• Albumin \> 3.0 g/dl
• Creatinine =\< 2.5 x ULN
• Serum potassium, magnesium and phosphorus \>= LLN and =\< 1.2 x ULN
• Total serum calcium \[corrected for serum albumin\] or ionized calcium \>= LLN
• Clinically euthyroid; patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
• Baseline MUGA or ECHO must demonstrate LVEF \>= the lower limit of the institutional normal

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Candidate for known standard therapy for the patient's disease that is potentially curative
• Uncontrolled infection requiring ongoing antibiotics
• Receiving corticosteroids \> 20mg of prednisone per day (or equivalent)
• Persistent toxicities \>= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
• Patients with congenital long QT syndrome
• History or presence of sustained ventricular tachyarrhythmia (patients with a history of atrial arrhythmia are eligible but should be discussed with the study PI prior to enrollment)
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR \< 50 bpm; patients with pacemakers are eligible if HR \>= 50 bpm
• Screening ECG with a QTcFredericia (QTcF) \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina =\< 6 months prior registration
• Other clinically significant heart disease (e.g. CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Pregnant women or women of reproductive ability who are unwilling to use effective contraception during the study and for 3 months after stopping treatment

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell, Peripheral; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Mycosis Fungoides; Sezary Syndrome; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

Panobinostat; Blotting, Western; Flow Cytometry; Immunohistochemistry

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Lymphoma, T-Cell, Cutaneous; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Electrophoresis; Chemistry Techniques, Analytical; Investigative Techniques; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Histocytochemistry; Histological Techniques

Results Point of Contact

• Title: Patrick Johnston, MD, PhD
• Organization: Mayo Clinic Cancer Center

johnston.patrick@mayo.edu

507-284-2511

Study Officials

• Patrick Johnston, M.D.

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

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: December 14, 2010
• First Posted: December 16, 2010
• Study Start: January 17, 2011
• Primary Completion: May 9, 2016
• Study Completion: December 2, 2019
• Last Updated: May 24, 2022
• Results First Posted: May 17, 2018

Record last verified: 2022-05

Locations

US (2)