Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
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
5 other identifiers
interventional
124
1 country
3
Brief Summary
This phase I/II trial studies the side effects and best dose of panobinostat and everolimus when given together and to see how well they work in treating patients with multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma that has come back. Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2009
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 1, 2009
CompletedStudy Start
First participant enrolled
June 1, 2009
CompletedFirst Posted
Study publicly available on registry
June 11, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedResults Posted
Study results publicly available
May 18, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 16, 2019
CompletedMarch 10, 2020
March 1, 2020
6.5 years
June 1, 2009
April 19, 2018
March 2, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of patients reporting a dose-limiting event are reported.
4 weeks
Overall Response Rate (Phase II)
For myeloma, a complete response(CR, defined as Negative immunofixation(IFE) of the serum and urine, \< 5% plasma cells in bone marrow(BM), Disappearance of plasmacytomas), stringent CR(sCR, defined as CR plus Normal serum FLC ratio, Absence of clonal cells in BM), very good partial response(VGPR, defined as PR plus Serum and urine M-component detectable by IFE but not on electrophoresis), partial response(PR, defined as a ≥ 50% reduction of serum M-protein and/or reduction in 24-h urinary M-protein by ≥ 90% or to \<200 mg per 24 h), or minor response(MR, defined as ≥25% but \< 49% reduction of serum M-protein and reduction in 24h urine M-protein by 50-89%) noted as the objective status. For lymphoma, a CR(defined as no evidence of measurable disease), or PR(defined as regression of measurable disease and no new sites of disease) noted as the objective status. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
Up to 12 courses
Secondary Outcomes (3)
Overall Survival Time (Phase II)
Time from registration to death due to any cause, assessed up to 2 years post-treatment
Progression-free Survival (Phase II)
Time from registration to progression or death due to any cause, assessed up to 2 years post-treatment
Duration of Response (Phase II)
The time from the date at which the patient's objective status is first noted to be a CR, sCR, VGPR, PR, or minor response to the earliest date progression is documented, assessed up to 2 years post-treatment
Other Outcomes (2)
Change in Pharmacologic (Pharmacokinetic/Pharmacodynamic) Parameters
Day 5 and 19 of the first course and then day 1 of each subsequent courses (courses 2-4) prior to the daily dose and 1 and 2 hours after each dose
Changes in Biological Markers
Baseline to up to 12 courses
Study Arms (1)
Treatment (panobinostat and everolimus)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Relapsed or refractory multiple myeloma requiring therapy, who have failed, unable to tolerate, or refused other available active therapies
- Biopsy-proven relapsed or refractory non-Hodgkin lymphoma or Hodgkin disease 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, 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 central nervous system \[CNS\] lymphoma at any time are not required to have a re-biopsy to be eligible for this study)
- Multiple myeloma:
- Serum monoclonal protein \>= 1.0 g/dL
- \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease) at time of registration
- Lymphoma:
- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (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
- +44 more criteria
You may not qualify if:
- Candidate for known standard therapy for the patient's disease that is potentially curative
- Uncontrolled infection
- Receiving corticosteroids \> 20 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone per day if they are being given for disorders other than lymphoma (with the exception of CNS lymphoma, which steroids are permitted at the lowest possible dose necessary and should not be escalated during treatment) such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma
- Persistent toxicities \>= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- 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 Sponsor prior to enrollment)
- Any history of ventricular fibrillation or torsade de pointes
- Bradycardia defined as heart rate (HR) \< 50 beats per minute (bpm;) patients with pacemakers are eligible if HR \>= 50 bpm
- Screening electrocardiogram (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 to starting study drug
- Other clinically significant heart disease (e.g., congestive heart failure \[CHF\] New York \[NY\] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Any of the following:
- Pregnant women or women of reproductive ability who are unwilling to use effective contraception
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
- National Cancer Institute (NCI)collaborator
Study Sites (3)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mark O Hatfield-Warren Grant Magnuson Clinical Center
Bethesda, Maryland, 20892, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Shaji Kumar, MD
- Organization
- Mayo Clinic Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Shaji Kumar
Mayo Clinic
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 1, 2009
First Posted
June 11, 2009
Study Start
June 1, 2009
Primary Completion
December 1, 2015
Study Completion
July 16, 2019
Last Updated
March 10, 2020
Results First Posted
May 18, 2018
Record last verified: 2020-03