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Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma


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.


Inclusion Criteria:



1. Histologically confirmed Hodgkin or non Hodgkin's lymphoma

2. Relapsed or refractory after standard treatments and with no curative option with
conventional therapy

3. No evidence of cerebral or meningeal involvement by lymphoma

4. Age >= 18 years

5. ECOG performance status 0 to 2

6. Life expectancy of at least 3 months

7. Signed informed consent form prior to enrollment

8. Patients must meet the following laboratory criteria: AST/SGOT and ALT/SGPT upper limit of normal (ULN) ) or to lymphoma involvement, Serum bilirubin free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)

9. Patients must have at least one measurable site of disease

10. Adequate bone marrow function as shown by: ANC >/= 1.0 x 109/L, Platelets >/=100 x
109/L

11. Fasting serum cholesterol patient can only be included after initiation of appropriate lipid lowering
medication 24 hours before starting therapy.

12. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days of the first administration of study drug

Exclusion Criteria:

1. Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small
lymphocytic lymphoma may be included)

2. Chemotherapy or radiation therapy or other investigational agents within 4 weeks
prior to entering the study

3. Previous radioimmunotherapy within 12 weeks

4. Prior therapy with HDAC or mTOR inhibitors i.e. temsirolimus, vorinostat (the list is
not inclusive of investigational agents in these classes of drugs)

5. Patient with known HIV infection

6. Known active viral hepatitis

7. 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

8. Impaired cardiac function including any one of the following: • Screening ECG with a
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.

9. 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

10. Concomitant use of drugs with a risk of causing torsades de pointes

11. Patients with unresolved diarrhea CTCAE grade 1

12. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral PANOBINOSTAT or everolimus.

13. 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.

14. Male patients whose sexual partners are WOCBP not using effective birth control

15. 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.

16. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis
C; baseline testing for HIV and hepatitis C is not required

17. Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent

18. 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.

19. Patients should not receive immunization with attenuated live vaccines within one
week of study registration or during study period

20. COPD or asthma requiring therapy

21. Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

22. Active (acute or chronic) uncontrolled severe infection, requiring oral or
intravenous antibiotics.

23. Patients receiving treatment on another clinical research trial.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)

Outcome Time Frame:

28 day treatment cycles

Safety Issue:

Yes

Principal Investigator

Yasuhiro Oki, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2008-0805

NCT ID:

NCT00967044

Start Date:

November 2009

Completion Date:

Related Keywords:

  • Lymphoma
  • Relapsed or Refractory Lymphoma
  • Hodgkin's lymphoma
  • Non Hodgkin's Lymphoma
  • NHL
  • LBH589
  • Panobinostat
  • RAD001
  • Everolimus
  • Lymphoma

Name

Location

University of Texas MD Anderson Cancer CenterHouston, Texas  77030