Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
|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: NCT00918333|
Recruitment Status : Active, not recruiting
First Posted : June 11, 2009
Last Update Posted : February 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|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 Non-Hodgkin Lymphoma Recurrent Adult Acute Lymphoblastic Leukemia 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 Chronic Lymphocytic Leukemia Refractory Multiple Myeloma Splenic Marginal Zone Lymphoma T-cell Adult Acute Lymphoblastic Leukemia Waldenström Macroglobulinemia||Drug: panobinostat Drug: everolimus Other: laboratory biomarker analysis Other: pharmacological study||Phase 1 Phase 2|
I. To determine the maximum tolerated doses (MTD) of LBH589 (panobinostat) and RAD001 (everolimus) when used in combination in patients with myeloma or lymphoma. (Phase I) II. To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory lymphoma. (Arm A, phase II) III. To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory multiple myeloma. (Arm B, phase II)
I. To describe the toxicities associated with the combination of LBH589 with RAD001. (Phase I) II. To further describe the toxicities associated with the combination of LBH589 with RAD001 in each arm independently. (Phase II) III. To evaluate overall survival, progression-free survival, and duration of response in each arm independently. (Phase II)
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.
OUTLINE: This is a phase I, dose-escalation study of panobinostat and everolimus followed by a phase II study. (dose-escalation closed to accrual as of April 6, 2011)
Patients receive panobinostat orally (PO) once daily (QD) or on days 1, 3, 5, 15, 17, and 19 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||148 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||June 2009|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: Treatment (panobinostat and everolimus)
Patients receive panobinostat PO QD or on days 1, 3, 5, 15, 17, and 19 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: everolimus
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
- MTD of everolimus and panobinostat, determined according to incidence of dose limiting toxicity assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (Phase I) [ Time Frame: 4 weeks ]Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Proportion of confirmed tumor responses in each arm (multiple myeloma and lymphoma) (Phase II) [ Time Frame: Up to 12 courses ]Defined to be a complete response (CR), complete response unconfirmed (Cru), stringent complete response (sCR), very good partial response (VGPR), or partial response (PR) noted as the objective status. Proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
- Survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years post-treatment ]Estimated using the method of Kaplan-Meier.
- Progression-free survival [ Time Frame: Time from registration to progression or death due to any cause, assessed up to 2 years post-treatment ]Estimated using the method of Kaplan-Meier.
- Duration of response [ Time Frame: The time from the date at which the patient's objective status is first noted to be a CR, CRu, sCR, VGPR, PR, or minor response to the earliest date progression is documented, assessed up to 2 years post-treatment ]Estimated using the method of Kaplan-Meier.
- Change in pharmacologic (pharmacokinetic/pharmacodynamic) parameters [ Time Frame: Baseline to day 5 and 19 and then day 1 of each subsequent courses (courses 2-4) and 1 and 2 hours after each dose ]Changes in parameters will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests, Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, these changes in pharmacologic markers and biological results will be explored in relation to clinical outcome to explore any differences between responders and non-responders.
- Changes in biological markers [ Time Frame: Baseline to up to 2 years ]Changes in parameters will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests, Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, these changes in pharmacologic markers and biological results will be explored in relation to clinical outcome to explore any differences between responders and non-responders.
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): NCT00918333
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Maryland|
|Mark O Hatfield-Warren Grant Magnuson Clinical Center|
|Bethesda, Maryland, United States, 20892|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Shaji Kumar||Mayo Clinic|