LymphomaPhase 1/2NCT00967044
Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
A Phase 1/2 study testing Panobinostat and Everolimus in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Objectives: Primary: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Panobinostat and Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Mar 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Histologically confirmed Hodgkin or non Hodgkin's lymphoma
- Relapsed or refractory after standard treatments and with no curative option with conventional therapy
- No evidence of cerebral or meningeal involvement by lymphoma
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Life expectancy of at least 3 months
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- Signed informed consent form prior to enrollment
- Patients must meet the following laboratory criteria: Aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) </= 2.5 * upper limit of normal (ULN) ) or </= 5.0 x ULN if the transaminase elevation is due to lymphoma involvement, Serum bilirubin </= 1.5 * ULN, Serum creatinine </=1.5 * ULN free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)
- Patients must have at least one measurable site of disease
- Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) >/= 1.0 x 109/L, Platelets >/=100 x 109/L
- Fasting serum cholesterol </=300 mg/dL OR </=7.75 mmol/L AND fasting triglycerides </= 2.5 * ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication 24 hours before starting therapy.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study drug
Who cannot join
- Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)
- Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study
- Previous radioimmunotherapy within 12 weeks
- Prior therapy with HDAC or [1] mammalian target of rapamycin (mTOR) inhibitors i.e. temsirolimus, vorinostat (the list is not inclusive of investigational agents in these classes of drugs)
- Patient with known HIV infection
- Known active viral hepatitis
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- Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study
- Impaired cardiac function including any one of the following: • Screening ECG with a corrected QT interval (QTc) > 450 msec confirmed by the investigator prior to enrollment to the study • Patients with congenital long QT syndrome • History of sustained ventricular tachycardia • Any history of ventricular fibrillation or torsades de pointes • Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate >= 50 beats per minute are eligible.
- Impaired cardiac function including any one of the following continued: • Patients with a myocardial infarction or unstable angina within 6 months from registration on study • Congestive heart failure (NY Heart Association class III or IV) • Right bundle branch block and left anterior hemiblock (bifascicular block) • Uncontrolled hypertension
- Concomitant use of drugs with a risk of causing torsades de pointes
- Patients with unresolved diarrhea Common Toxicity Criteria for Adverse Effects (CTCAE) grade 1
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral PANOBINOSTAT or everolimus.
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
- Male patients whose sexual partners are WOCBP not using effective birth control
- Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, basal or squamous cell carcinoma of the skin, or early stage prostate carcinoma.
- Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone <= 20 mg. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study registration or during study period
- Chronic obstructive pulmonary disease (COPD) or asthma requiring therapy
- Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- Active (acute or chronic) uncontrolled severe infection, requiring oral or intravenous antibiotics.
- Patients receiving treatment on another clinical research trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
Objectives:
Primary:
Read more
- Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin).
- Determine the safety and efficacy of this novel combination in a phase-II study in patients with relapsed Hodgkin and non-Hodgkin lymphoma
Secondary:
- Determine the in vivo effect of therapy on selected serum cytokines/chemokines (TGF-beta, thymus and activation-regulated chemokine (TARC), IL-6, IL-10, VEGF).
- Examine pre-treatment level of selected molecular targets (HDACs 1-11, STAT6, pSTAT6, STAT3, pSTAT3, Myc, Akt, Pichia anomala killer toxin (pAkt), S6, pS6, p21, cyclin D1) in primary lymphoma cells and the surrounding reactive inflammatory cells obtained by core needle biopsies from patients with relapsed lymphoma.
- Examine the correlation between molecular and biologic markers and clinical response and/or treatment-related toxicity.
Read the detailed description
Phase I:
The Study Drugs:
Both panobinostat and everolimus are designed to block cancer cells from multiplying. Everolimus may also stop the growth of new blood vessels that help tumor growth. As a result, the cancer cells may grow more slowly or die.
Study Groups:
If you are found to be eligible to take part in this phase of the study, you will be assigned to a study group based on when you joined this study. Up to 5 groups of 3-6 participants will be enrolled in this phase of the study.
If you are enrolled in this phase of the study, the dose of study drugs you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the study drugs. Each new group may receive a higher dose of study drugs than the group before it, if no intolerable side effects were seen. This will continue for up to 5 combinations of the study drugs, until the highest tolerable dose of study drugs in combination is found.
Up to 2 dose levels of everolimus and up to 4 dose levels of panobinostat will be tested in this phase of the study. This is up to 5 different dose combinations of everolimus and panobinostat. (The dose of both drugs does not get raised in every dose level, but sometimes only 1 drug's dose gets raised.)
Study Drug Administration:
Panobinostat:
You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study are 28 days long.
You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day that you take it.
If you miss a dose of panobinostat, take it as soon as you remember it on the same day. However, if more than 12 hours have passed since you were supposed to take the dose, you should skip that day's dose. In that case, wait to take panobinostat until the next scheduled treatment day.
Everolimus:
You will take everolimus every day, at about the same time in the morning. You will take it by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or drink except water ("fasting") or with no more than a light, fat-free meal.
Examples of light, fat-free meals include cereal with fat-free milk, a fat-free muffin, toast, a bagel with fat-free spread, or fruit salad.
The reason to avoid high-fat breakfasts while you are taking everolimus is to help the drug get absorbed better by your body.
If you experience intolerable side effects, you must call your doctor right away. The doctor may then lower the dose of study drug or take you off study.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
- You will be asked about any drugs you may be taking.
- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Day 1 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn for biomarker research.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Days 1 and 5 of Cycle 1, you will have an ECG.
On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine tests.
On Week 2 of Cycle 1, blood (about 1 teaspoon) will be drawn for biomarker research.
On Day 1 of Cycle 2 and every cycle after that:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
Every 8 weeks:
- You will have a PET scan to check the status of the disease.
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
Length of Study:
If you show benefit from taking the study drugs, you may receive up to 6 cycles. You will be taken off study if you have intolerable side effects or the disease gets worse.
End-of-Treatment Visit:
After you stop taking the study drugs, you will return to the clinic for an end-of-treatment visit:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECG.
- You will be asked about any drugs you may be taking.
- Blood (about 3 1/2 teaspoons) will be collected for routine tests.
- You will have a PET scan to check the status of the disease.
- You will have a computed tomography (CT) scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- If the doctor thinks the disease has responded completely, you will have a bone marrow biopsy and aspiration to confirm the complete response. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
This is an investigational study. Panobinostat is not FDA approved or commercially available. At this time the drug is being used in research only. Everolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Using everolimus in combination with panobinostat in patients with lymphoma is investigational.
Up to 18 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
Phase II:
The Study Drugs:
Both panobinostat and everolimus are designed to block cancer cells from multiplying. Everolimus may also stop the growth of new blood vessels that help tumor growth. As a result, the cancer cells may grow more slowly or die.
Study Drug Administration:
Panobinostat:
You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study are 28 days long.
You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day that you take it.
If you miss a dose of panobinostat, take it as soon as you remember it on the same day. However, if more than 12 hours have passed since you were supposed to take the dose, you should skip that day's dose. In that case, wait to take panobinostat until the next scheduled treatment day.
Everolimus:
You will take everolimus every day, at about the same time in the morning. You will take it by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or drink except water ("fasting") or with no more than a light, fat-free meal.
Examples of light, fat-free meals include cereal with fat-free milk, a fat-free muffin, toast, a bagel with fat-free spread, or fruit salad.
The reason to avoid high-fat breakfasts while you are taking everolimus is to help the drug get absorbed better by your body.
If you experience intolerable side effects, you must call your doctor right away. The doctor may then lower the dose of study drug or take you off study.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
- You will be asked about any drugs you may be taking.
- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Day 1 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn for biomarker research (if blood was not drawn for biomarker research at screening).
- If your doctor thinks it is needed, urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Days 1 and 5 of Cycle 1, you will have an ECG.
On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine tests.
On Weeks 2 and 3 of Cycle 1, blood (about 4 tablespoons) will be drawn for biomarker research.
On Day 1 of Cycle 2 and every cycle after that:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
Every 8 weeks:
- You will have a PET scan to check the status of the disease.
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
Length of Study:
You may continue receiving the study drugs for as long as you are benefitting. You will be taken off study if you have intolerable side effects or the disease gets worse.
End-of-Treatment Visit:
After you stop taking the study drugs, you will return to the clinic for an end-of-treatment visit:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECG.
- You will be asked about any drugs you may be taking.
- Blood (about 3 1/2 teaspoons) will be collected for routine tests.
- You will have a PET scan to check the status of the disease.
- You will have a computed tomography (CT) scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- If the doctor thinks the disease has responded completely, you will have a bone marrow biopsy and aspiration to confirm the complete response. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
This is an investigational study. Panobinostat is not FDA approved or commercially available. At this time the drug is being used in research only. Everolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Using everolimus in combination with panobinostat in patients with lymphoma is investigational.
Up to 42 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
- Conditions
- Lymphoma
- Being tested
- Panobinostat, Everolimus
- Keywords
- Relapsed or Refractory Lymphoma, Hodgkin's lymphoma, Non Hodgkin's Lymphoma, NHL, LBH589, Panobinostat, RAD001, Everolimus
- Medical subject headings
- Lymphoma, Recurrence, Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week
EverolimusDrug
Also called Afinitor, RAD001
Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat + Everolimus | Experimental | Panobinostat (LBH589) Plus Everolimus (RAD001) Receives: Drug: Panobinostat; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
MTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.
Measured: 28 day treatment cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2009 (estimated)
- Study startNov 2009
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Yasuhiro Oki, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00967044
- Sponsor's protocol ID
- 2008-0805
- Other IDs
- NCI-2011-03023
- Status last verified
- Feb 2015
- First submitted
- 25 Aug 2009
- Last updated
- 26 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
- ClinicalTrials.gov ID
- NCT00967044
- Acronym / sponsor ID
- 2008-0805
- Conditions
- Lymphoma
- Keywords
- Relapsed or Refractory Lymphoma, Hodgkin's lymphoma, Non Hodgkin's Lymphoma, NHL, LBH589, Panobinostat, RAD001, Everolimus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Nov 2009
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 27 Aug 2009 (estimated)
- Results
- Posted 10 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives:
Primary:
- Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin).
- Determine the safety and efficacy of this novel combination in a phase-II study in patients with relapsed Hodgkin and non-Hodgkin lymphoma
Secondary:
- Determine the in vivo effect of therapy on selected serum cytokines/chemokines (TGF-beta, thymus and activation-regulated chemokine (TARC), IL-6, IL-10, VEGF).
- Examine pre-treatment level of selected molecular targets (HDACs 1-11, STAT6, pSTAT6, STAT3, pSTAT3, Myc, Akt, Pichia anomala killer toxin (pAkt), S6, pS6, p21, cyclin D1) in primary lymphoma cells and the surrounding reactive inflammatory cells obtained by core needle biopsies from patients with relapsed lymphoma.
- Examine the correlation between molecular and biologic markers and clinical response and/or treatment-related toxicity.
Detailed description
Phase I:
The Study Drugs:
Both panobinostat and everolimus are designed to block cancer cells from multiplying. Everolimus may also stop the growth of new blood vessels that help tumor growth. As a result, the cancer cells may grow more slowly or die.
Study Groups:
If you are found to be eligible to take part in this phase of the study, you will be assigned to a study group based on when you joined this study. Up to 5 groups of 3-6 participants will be enrolled in this phase of the study.
If you are enrolled in this phase of the study, the dose of study drugs you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the study drugs. Each new group may receive a higher dose of study drugs than the group before it, if no intolerable side effects were seen. This will continue for up to 5 combinations of the study drugs, until the highest tolerable dose of study drugs in combination is found.
Up to 2 dose levels of everolimus and up to 4 dose levels of panobinostat will be tested in this phase of the study. This is up to 5 different dose combinations of everolimus and panobinostat. (The dose of both drugs does not get raised in every dose level, but sometimes only 1 drug's dose gets raised.)
Study Drug Administration:
Panobinostat:
You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study are 28 days long.
You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day that you take it.
If you miss a dose of panobinostat, take it as soon as you remember it on the same day. However, if more than 12 hours have passed since you were supposed to take the dose, you should skip that day's dose. In that case, wait to take panobinostat until the next scheduled treatment day.
Everolimus:
You will take everolimus every day, at about the same time in the morning. You will take it by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or drink except water ("fasting") or with no more than a light, fat-free meal.
Examples of light, fat-free meals include cereal with fat-free milk, a fat-free muffin, toast, a bagel with fat-free spread, or fruit salad.
The reason to avoid high-fat breakfasts while you are taking everolimus is to help the drug get absorbed better by your body.
If you experience intolerable side effects, you must call your doctor right away. The doctor may then lower the dose of study drug or take you off study.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
- You will be asked about any drugs you may be taking.
- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Day 1 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn for biomarker research.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Days 1 and 5 of Cycle 1, you will have an ECG.
On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine tests.
On Week 2 of Cycle 1, blood (about 1 teaspoon) will be drawn for biomarker research.
On Day 1 of Cycle 2 and every cycle after that:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
Every 8 weeks:
- You will have a PET scan to check the status of the disease.
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
Length of Study:
If you show benefit from taking the study drugs, you may receive up to 6 cycles. You will be taken off study if you have intolerable side effects or the disease gets worse.
End-of-Treatment Visit:
After you stop taking the study drugs, you will return to the clinic for an end-of-treatment visit:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECG.
- You will be asked about any drugs you may be taking.
- Blood (about 3 1/2 teaspoons) will be collected for routine tests.
- You will have a PET scan to check the status of the disease.
- You will have a computed tomography (CT) scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- If the doctor thinks the disease has responded completely, you will have a bone marrow biopsy and aspiration to confirm the complete response. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
This is an investigational study. Panobinostat is not FDA approved or commercially available. At this time the drug is being used in research only. Everolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Using everolimus in combination with panobinostat in patients with lymphoma is investigational.
Up to 18 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
Phase II:
The Study Drugs:
Both panobinostat and everolimus are designed to block cancer cells from multiplying. Everolimus may also stop the growth of new blood vessels that help tumor growth. As a result, the cancer cells may grow more slowly or die.
Study Drug Administration:
Panobinostat:
You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study are 28 days long.
You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day that you take it.
If you miss a dose of panobinostat, take it as soon as you remember it on the same day. However, if more than 12 hours have passed since you were supposed to take the dose, you should skip that day's dose. In that case, wait to take panobinostat until the next scheduled treatment day.
Everolimus:
You will take everolimus every day, at about the same time in the morning. You will take it by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or drink except water ("fasting") or with no more than a light, fat-free meal.
Examples of light, fat-free meals include cereal with fat-free milk, a fat-free muffin, toast, a bagel with fat-free spread, or fruit salad.
The reason to avoid high-fat breakfasts while you are taking everolimus is to help the drug get absorbed better by your body.
If you experience intolerable side effects, you must call your doctor right away. The doctor may then lower the dose of study drug or take you off study.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
- You will be asked about any drugs you may be taking.
- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Day 1 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn for biomarker research (if blood was not drawn for biomarker research at screening).
- If your doctor thinks it is needed, urine will be collected for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
On Days 1 and 5 of Cycle 1, you will have an ECG.
On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine tests.
On Weeks 2 and 3 of Cycle 1, blood (about 4 tablespoons) will be drawn for biomarker research.
On Day 1 of Cycle 2 and every cycle after that:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs you may be taking and any side effects that may have occurred.
- Your performance status will be recorded.
- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
Every 8 weeks:
- You will have a PET scan to check the status of the disease.
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
Length of Study:
You may continue receiving the study drugs for as long as you are benefitting. You will be taken off study if you have intolerable side effects or the disease gets worse.
End-of-Treatment Visit:
After you stop taking the study drugs, you will return to the clinic for an end-of-treatment visit:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECG.
- You will be asked about any drugs you may be taking.
- Blood (about 3 1/2 teaspoons) will be collected for routine tests.
- You will have a PET scan to check the status of the disease.
- You will have a computed tomography (CT) scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.
- If your doctor thinks it is needed, urine will be collected for routine tests.
- If the doctor thinks the disease has responded completely, you will have a bone marrow biopsy and aspiration to confirm the complete response. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy test.
This is an investigational study. Panobinostat is not FDA approved or commercially available. At this time the drug is being used in research only. Everolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Using everolimus in combination with panobinostat in patients with lymphoma is investigational.
Up to 42 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Panobinostat + Everolimus | Experimental | Drug: Panobinostat, Drug: EverolimusPanobinostat (LBH589) Plus Everolimus (RAD001) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed Hodgkin or non Hodgkin's lymphoma
- Relapsed or refractory after standard treatments and with no curative option with conventional therapy
- No evidence of cerebral or meningeal involvement by lymphoma
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Key exclusion criteria (23 listed)
- Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)
- Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study
- Previous radioimmunotherapy within 12 weeks
- Prior therapy with HDAC or [1] mammalian target of rapamycin (mTOR) inhibitors i.e. temsirolimus, vorinostat (the list is not inclusive of investigational agents in these classes of drugs)
- Patient with known HIV infection
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 |
|---|---|---|
| PanobinostatAlso: LBH589Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week | Drug | Panobinostat + Everolimus |
| EverolimusAlso: Afinitor, RAD001Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal. | Drug | Panobinostat + Everolimus |
Primary outcome
Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
Time frame: 28 day treatment cycle
MTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Yasuhiro Oki, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat and Everolimus in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site 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?
The sponsor lists 12 inclusion and 23 exclusion criteria. 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 26 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (MTD) of Everolimus With Panobinostat (time frame: 28 day treatment cycle). 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 26 Feb 2015.