LymphomaPhase 1NCT00962507
Panobinostat and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
A Phase 1 study testing everolimus, panobinostat and laboratory biomarker analysis in people with Lymphoma and Multiple Myeloma and Plasma Cell Neoplasm, run by City of Hope Medical Center at 2 sites in United States.
Trial summary
RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving panobinostat together with everolimus may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- everolimus, panobinostat and laboratory biomarker analysis
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2009to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of one of the following:
- Hodgkin or non-Hodgkin lymphoma (including small lymphocytic lymphoma [SLL])
- Any histology, including B, T, or NK/T cell allowed
- Multiple myeloma (MM)
- Relapsed or refractory disease
- Patients with lymphoma must have relapsed after or be refractory to an upfront regimen (e.g., CHOP or ABVD) and a salvage regimen (e.g., ICE or ESHAP)
- Patients with SLL should have relapsed after a fludarabine-containing regimen
- Patients with MM must have progressed within 100 days after receiving a regimen containing bortezomib and either thalidomide or lenalidomide AND have a 25% increase in serum paraproteins, urinary light chains, or plasma cell number in the bone marrow
- No active CNS disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³ (transfusion allowed in patients with biopsy-proven bone marrow involvement)
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to leukemic involvement)
- Serum bilirubin ≤ 1.5 times ULN
- Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
- Serum potassium normal
- Serum phosphorous normal
- Serum total calcium (corrected for serum albumin) or serum ionized calcium normal
- Serum magnesium normal
- TSH and free T4 normal (thyroid hormone replacement allowed)
- Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤ 2.5 times ULN (elevated levels allowed provided an appropriate lipid-lowering medication has been initiated)
- LVEF normal by MUGA or ECHO
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method (including barrier method) contraception during and for 3 months after completion of study treatment
- No impaired cardiac function, including any of the following:
- QTc > 450 msec by screening ECG
- Congenital long QT syndrome
- History of sustained ventricular tachycardia
- History of ventricular fibrillation or torsades de pointes
- Bradycardia, defined as heart rate (HR) < 50 beats/min (pacemaker allowed provided HR ≥ 50 beats/min)
- Myocardial infarction or unstable angina within the past 6 months
- NYHA class III-IV congestive heart failure
- Right bundle branch block and left anterior hemiblock (bifascicular block)
- No uncontrolled hypertension
- No unresolved diarrhea > CTCAE grade 1
- No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- No other concurrent severe or uncontrolled medical condition
- No other primary malignancy within the past 5 years other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
- No known HIV or hepatitis C positivity
- No significant history of non-compliance to medical regimens
- No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or temsirolimus), or their excipients
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior autologous or allogeneic stem cell transplantation allowed
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
- More than 1 week since prior and no concurrent immunization with live attenuated vaccines
- More than 4 weeks since prior valproic acid
- No other prior histone deacetylase inhibitors
- No concurrent chronic systemic corticosteroids or another immunosuppressive agent, other than for control of itching (as in cutaneous T-cell lymphoma)
- Concurrent corticosteroids allowed provided patient has been on a stable dosage regimen for ≥ 2 weeks before study entry
- Topical or inhaled corticosteroids allowed
- No concurrent drugs that may induce torsades de pointes
- No concurrent CYP3A4 inhibitors
- No concurrent radiotherapy or other anticancer therapy
- No concurrent grapefruit, grapefruit juice, or seville (sour) oranges
- No concurrent medications that may cause QTc prolongation
- No other concurrent investigational therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope Medical Center
Duarte, California, 91010-3000
City of Hope Medical Group
Pasadena, California, 91105
About this study
Official title: A Phase I Study Evaluating the Combination of the Deacetylase Inhibitor, LBH589 Plus the mTOR Inhibitor RAD001, in Relapsed and Refractory Adult Patients With Lymphoma
RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving panobinostat together with everolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with everolimus in treating patients with relapsed or refractory lymphoma or multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the safety and feasibility of combining panobinostat with everolimus in patients with recurrent or refractory lymphoma or multiple myeloma.
- To define the maximum tolerated dose of panobinostat in combination with everolimus in these patients.
Secondary
- To obtain preliminary data for response to this treatment regimen in these patients.
- To perform correlative studies relevant to this treatment regimen.
OUTLINE: This is a dose-escalation study of panobinostat.
Patients receive oral panobinostat 3 days a week and oral everolimus once every other day for 4 weeks Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Blood and bone marrow samples may be collected for pharmacokinetic and correlative laboratory studies.
After completion of study treatment, patients are followed up for ≥ 4 weeks.
- Being tested
- everolimus, panobinostat, laboratory biomarker analysis, pharmacological study
- Keywords
- recurrent adult T-cell leukemia/lymphoma, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
- Medical subject headings
- Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Beginning with 5 mg every other day Monday, Wednesday or Friday for a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment.
panobinostatDrug
10 mg every Monday and Thursday of a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment.
laboratory biomarker analysisOther
Pre-study, day 1 and day 26 samples to evaluation how the study drugs work in vitro (in a test tube).
Pre-study, day 1 and day 26
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Measured: 90 days post treatment start
Toxicity
Measured: 90 days post treatment start
Secondary outcomes (1)
Pharmacokinetic and correlative studies
Measured: Day 1 and Day 26 of the first cycle of treament
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Leslie Popplewell, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00962507
- Sponsor's protocol ID
- 08099
- Other IDs
- P30CA033572, CHNMC-08099, NOVARTIS-CHNMC-08099, CDR0000652208, NCI-2010-00259
- Status last verified
- Feb 2013
- First submitted
- 19 Aug 2009
- Last updated
- 15 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating the Combination of the Deacetylase Inhibitor, LBH589 Plus the mTOR Inhibitor RAD001, in Relapsed and Refractory Adult Patients With Lymphoma
- ClinicalTrials.gov ID
- NCT00962507
- Acronym / sponsor ID
- 08099
- Keywords
- recurrent adult T-cell leukemia/lymphoma, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult Hodgkin lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 20 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving panobinostat together with everolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with everolimus in treating patients with relapsed or refractory lymphoma or multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- To evaluate the safety and feasibility of combining panobinostat with everolimus in patients with recurrent or refractory lymphoma or multiple myeloma.
- To define the maximum tolerated dose of panobinostat in combination with everolimus in these patients.
Secondary
- To obtain preliminary data for response to this treatment regimen in these patients.
- To perform correlative studies relevant to this treatment regimen.
OUTLINE: This is a dose-escalation study of panobinostat.
Patients receive oral panobinostat 3 days a week and oral everolimus once every other day for 4 weeks Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Blood and bone marrow samples may be collected for pharmacokinetic and correlative laboratory studies.
After completion of study treatment, patients are followed up for ≥ 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusBeginning with 5 mg every other day Monday, Wednesday or Friday for a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment. | Drug | – |
| panobinostat10 mg every Monday and Thursday of a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment. | Drug | – |
| laboratory biomarker analysisPre-study, day 1 and day 26 samples to evaluation how the study drugs work in vitro (in a test tube). | Other | – |
| pharmacological studyPre-study, day 1 and day 26 | Other | – |
Primary outcome
Maximum tolerated dose
Time frame: 90 days post treatment start
Toxicity
Time frame: 90 days post treatment start
1 secondary outcome
Pharmacokinetic and correlative studies
Time frame: Day 1 and Day 26 of the first cycle of treament
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie Popplewell, MD principal investigator
City of Hope Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing everolimus, panobinostat and laboratory biomarker analysis in people with Lymphoma and Multiple Myeloma and Plasma Cell Neoplasm, run by City of Hope Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 90 days post treatment start). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2013.