Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of panobinostat and everolimus when given together and to see how well they work in treating patients with recurrent multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma.
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
B-cell Adult Acute Lymphoblastic Leukemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Primary Central Nervous System Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Multiple Myeloma
Splenic Marginal Zone Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
Other: laboratory biomarker analysis
Other: pharmacological study
Other: flow cytometry
Other: immunohistochemistry staining method
Other: western blotting
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of the Histone Deacetylase (HDAC) Inhibitor LBH589 (Panobinostat) in Combination With mTOR Inhibitor RAD001 (Everolimus) in Patients With Relapsed Multiple Myeloma or Lymphoma|
- Toxicity, as assessed by NCI CTCAE v3.0 (phase I) [ Designated as safety issue: Yes ]
- Proportion of confirmed tumor responses (i.e., CR, CRu, sCR, VGPR, or PR) (phase II) [ Time Frame: Using up to 12 cycles of treatment ] [ Designated as safety issue: No ]
- Survival time [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Pharmacologic (pharmacokinetic/pharmacodynamic) parameters and biological (correlative laboratory) results and correlation to differences between responders and non-responders [ Time Frame: Before and after treatment ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral panobinostat (Monday, Wednesday, Friday) and oral everolimus once daily.
Other Names:Drug: everolimus
Other Names:Other: laboratory biomarker analysis Other: pharmacological study
Other Name: pharmacological studiesOther: flow cytometry Other: immunohistochemistry staining method
Other Name: immunohistochemistryOther: western blotting
I. To determine the maximum tolerated doses (MTD) of LBH589 and RAD001 when used in combination in patients with myeloma or lymphoma (Phase I).
II. Arm A: To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory lymphoma. (Phase II)
III. Arm B: To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory multiple myeloma (Phase II)
I. To further describe the toxicities associated with the combination of LBH589 with RAD001 in each arm independently.
II. To evaluate overall survival, progression-free survival, and duration of response in each arm independently.
I. To evaluate the pharmacokinetic interaction of LBH589 and RAD001.
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.
Patients receive oral panobinostat and oral everolimus once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed periodically for 2 years.
|United States, Arizona|
|Mayo Clinic Scottsdale-Phoenix||Active, not recruiting|
|Scottsdale, Arizona, United States, 85259|
|United States, Maryland|
|Metabolism Branch, NCI, NIH||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Ola Landgren, M.D., Ph.D. 301-496-0670 email@example.com|
|Principal Investigator: Ola Landgren, M.D., Ph.D.|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Mayo Clinic Clinical Trials Office 507-538-7623|
|Principal Investigator: Shaji K. Kumar, M.D.|
|Study Chair:||Shaji K. Kumar, M.D.||Mayo Clinic|
|Principal Investigator:||Joseph R. Mikhael, M.D.||Mayo clinic in Arizona|