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

Phase 2

Completed

Conditions: Adult Nasal Type Extranodal NK/T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Splenic Marginal Zone Lymphoma
Waldenstrom Macroglobulinemia
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma

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

Registration Number: NCT01261247

Lead Sponsor: Mayo Clinic

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

Detailed Description: PRIMARY OBJECTIVES: I. To evaluate the proportion of confirmed response of LBH589 in patients with relapsed or refractory non-Hodgkin lymphoma. SECONDARY OBJECTIVES: I. To describe the toxicities associated with LBH589 in patients with NHL. II. To evaluate overall survival, progression-free survival, and duration of response in patients treated with LBH589. TERTIARY OBJECTIVES: I. To evaluate the pharmacokinetics of LBH589. II. To assess the correlation between clinical (toxicity and/or tumor response or activity) effects with the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative laboratory) results. OUTLINE: 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. After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	pharmacological study	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.
Arm I	laboratory biomarker analysis	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.
Arm I	western blotting	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.
Arm I	DNA analysis	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.
Arm I	flow cytometry	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.
Arm I	immunohistochemistry staining method	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.
Arm I	panobinostat	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Confirmed Responses Defined to be a CR or PR Noted as the Objective Status	Every 28 days for up to 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival Time	Every 6 months for up to 2 years	The median overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Median Progression-free Survival Time	Every 6 months for up to 2 years	The median progression-free survival time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined using the Cheson et al. Revised Response Criteria for Malignant Lymphoma as: Any new lesion or increase by ≥50% of previously involved sites from nadir, Appearance of a new lesion(s) \> 1.5 cm in any axis, ≥50% increase from nadir in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node \> 1 cm in short axis, Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy, \> 50% increase from nadir in the SPD of any previous lesions, New or recurrent involvement.
Duration of Response	Every 6 months for up to 2 years	Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by ≥50% of previously involved sites from nadir).