Panobinostat Plus Ifosfamide, Carboplatin, and Etoposide (ICE) Compared With ICE For Relapsed Hodgkin Lymphoma

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01169636
Collaborator
Novartis (Industry)
62
1
3
75.5
0.8

Study Details

Study Description

Brief Summary

Objectives:
Primary objective:
  • Phase-I: To determine the maximal tolerated dose (MTD) of panobinostat (LBH589) + Ifosfamide + Mesna, Carboplatin and Etoposide (ICE) combination

  • Randomized Phase-II: To estimate the complete response (CR) rate in patients with relapsed and refractory classical Hodgkins Lymphoma (HL) receiving ICE versus PANOBINOSTAT plus ICE therapy

Secondary Objectives:
  • To assess the safety and tolerability of the novel combination of PANOBINOSTAT (LBH589) plus ICE versus ICE in patients with relapsed and refractory HL

  • To estimate the overall response rate (CR + partial response PR)

  • To estimate the success rate of stem cell collection in patients eligible for stem cell transplant

  • To estimate the percentage of patients who subsequently undergo autologous stem cell transplantation (ASCT)

  • To estimate the event free survival (EFS) at 1 year after randomization

  • To determine pretreatment expression level of histone deacetylases (HDAC1), HDAC2, and pSTAT3 and Signal transducer and activator of transcription protein (pSTAT6) by Immunohistochemistry (IHC) and correlate the results with treatment response

Detailed Description

Phase I:
The Study Drugs:

Panobinostat is designed to block the function of enzymes that are found inside cancer cells. These enzymes trigger cells to grow and multiply out of control. By blocking these enzymes, it may slow down the growth of or kill cancer cells.

Ifosfamide is designed to slow or stop the growth of cancer cells.

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Etoposide is designed to block cell growth.

Baseline Tests:

If you are found to be eligible to take part in this study, the following tests and procedures will be performed about 7 days before the first dose of the study drug:

  • You will have a physical exam, including measurement of your height, weight, and vital signs (blood pressure and heart rate).

  • You will have 1 electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

  • Blood (about 2 1/2 teaspoons) will be drawn for routine tests.

  • Women who are able to become pregnant must have a negative blood (about 1 1/2 teaspoons) pregnancy test.

Study Groups:

You will be assigned to a dose level of panobinostat based on when you join this study. Up to 2 dose levels of panobinostat will be tested. Up to 6participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of panobinostat is found.

All participants will receive the same dose level of ICE.

Once the highest tolerable dose is found, up to 20 extra participants, called the expansion group, will receive the study drugs at that dose.

Study Drug Administration:

Each cycle is 14 days.

ICE Administration:

On Day 1 (+/- 2 days) of Cycles 1-3, you will receive ifosfamide by vein over 24 hours.

On Day 1 (+/- 2 days) of Cycles 1-3, you will receive carboplatin by vein over 1 hour.

On Days 1-3 (+/- 2 days) of Cycles 1-3, you will receive etoposide by vein over 2 hours.

You will also receive mesna to help prevent side effects. On Day 2 (+/- 2 days) of Cycles 1-3, you will receive mesna by vein over 12 hours.

You will also receive pegfilgrastim to help prevent side effects. Beginning 24-48 hours after the completion of chemotherapy of Cycles 1-3, you will take pegfilgrastim through a needle under the skin.

Panobinostat Administration:

You will take panobinostat by mouth starting Day -6 of Cycle 1 (6 days before your first dose of ICE). You will take the panobinostat on Days -6, -4, and -2 of Cycle 1 and Days 1, 3, 5, 8, 10, and 12 of Cycles 1 and 2.

If you are in the expansion group, you will take panobinostat by mouth starting Day -6 of Cycle 1 (6 days before your first dose of ICE). You will take the panobinostat on Days -6, -4, and -2 of Cycle 1 and Days 1, 3, and 5 of Cycles 1 and 2.

You should take panobinostat around the same time each day with 1 cup (8 ounces) of water. You should swallow the capsules whole and not chew them. You must avoid grapefruit or grapefruit juice and seville (sour) oranges while on study.

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 dosing day.

Study Visits:

On Days -6 and -2 of Cycle 1, you will have 2 ECGs.

Within 7 days before each ICE therapy:
  • You will have a physical exam, including measurement of your height, weight, and vital signs.

  • Blood (about 2 1/2 teaspoons) will be drawn for routine tests.

  • You will be asked if you have had any side effects.

One (1) time a week, blood (2 1/2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 2 and beyond, you will have an ECG.

After Cycle 3:
  • You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.

  • If your bone marrow was positive at screening, you will have a positron emission tomography (PET) scan to check the status of the disease.

Length of Study:

You be on study for up to 3 cycles (about 42 days). You will be taken off study early if the disease worsens or you experience intolerable side effects.

End-of-Study Visit:

After you are off study, you will have an end-of-study visit at which the following will be performed:

You will have a physical exam, including measurement of your weight and vital signs.

You will have an ECG.

This is an investigational study. Panobinostat is not FDA approved or commercially available. It is currently being used for research purposes only.

ICE is FDA approved and commercially available for the treatment of several types of lymphoma, including relapsed and refractory Hodgkins lymphoma. The combination of panobinostat and ICE for the treatment of Hodgkin's lymphoma is investigational.

Up to 102 patients will take part in this study. All will be enrolled at MD Anderson.

Phase II:
The Study Drugs:

Panobinostat is designed to block the function of enzymes that are found inside cancer cells. These enzymes trigger cells to grow and multiply out of control. By blocking these enzymes, it may slow down the growth of or kill cancer cells.

Ifosfamide is designed to slow or stop the growth of cancer cells.

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Etoposide is designed to block cell growth.

Baseline Tests:

If you are found to be eligible to take part in this study, the following tests and procedures will be performed about 7 days before the first dose of the study drug:

  • You will have a physical exam, including measurement of your height, weight, and vital signs (blood pressure and heart rate).

  • You will have 1 electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

  • Blood (about 2 1/2 teaspoons) will be drawn for routine tests.

  • Women who are able to become pregnant must have a negative blood (about 1 1/2 teaspoons) pregnancy test.

Study Groups:

You will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.

  • If you are in Group 1, you will receive ICE.

  • If you are in Group 2, you will receive ICE and panobinostat.

Study Drug Administration:

Each cycle is 14 days.

ICE Administration:

On Day 1 (+/- 2 days) of Cycles 1-3, you will receive ifosfamide by vein over 24 hours.

On Day 1 (+/- 2 days) of Cycles 1-3, you will receive carboplatin by vein over 1 hour.

On Days 1-3 (+/- 2 days) of Cycles 1-3, you will receive etoposide by vein over 2 hours.

You will also receive mesna to help prevent side effects. On Day 2 (+/- 2 days) of Cycles 1-3, you will receive mesna by vein over 12 hours.

You will also receive pegfilgrastim to help prevent side effects. Beginning 24-48 hours after the completion of chemotherapy of Cycles 1-3, you will take pegfilgrastim through a needle under the skin.

Panobinostat Administration:

If you are in a group that will receive panobinostat, you will take panobinostat by mouth starting Day -6 of Cycle 1 (6 days before your first dose of ICE). You will take the panobinostat on 3 times a week during Cycles 1 and 2 (Days -6, -4, and -2 of Cycle 1 and Days 1, 3, and 5 Cycles 1 and 2).

You should take panobinostat around the same time each day with 1 cup (8 ounces) of water. You should swallow the capsules whole and not chew them. You must avoid grapefruit or grapefruit juice and seville (sour) oranges while on study.

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 dosing day.

Study Visits:

On Days -6 and -2 of Cycle 1, you will have 2 ECGs.

Within 7 days before each ICE therapy:
  • You will have a physical exam, including measurement of your height, weight, and vital signs.

  • Blood (about 2 1/2 teaspoons) will be drawn for routine tests.

  • You will be asked if you have had any side effects.

One (1) time a week, blood (2 1/2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 2 and beyond, you will have an ECG.

After Cycle 3:
  • You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the status of the disease.

  • If your bone marrow was positive at screening, you will have a PET scan to check the status of the disease.

Length of Study:

You be on study for up to 3 cycles (about 42 days). You will be taken off study early if the disease worsens or you experience intolerable side effects.

End-of-Study Visit:

After you are off study, you will have an end-of-study visit at which the following will be performed:

  • You will have a physical exam, including measurement of your weight and vital signs.

  • You will have an ECG.

This is an investigational study. Panobinostat is not FDA approved or commercially available. It is currently being used for research purposes only.

ICE is FDA approved and commercially available for the treatment of several types of lymphoma, including relapsed and refractory Hodgkins lymphoma. The combination of panobinostat and ICE for the treatment of Hodgkin's lymphoma is investigational.

Up to 102 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
62 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Study of Panobinostat Plus ICE Chemotherapy Followed by a Randomized Phase-II Study of ICE Compared With Panobinostat Plus ICE for Patients With Relapsed and Refractory Classical Hodgkin Lymphoma
Actual Study Start Date :
Jan 31, 2011
Actual Primary Completion Date :
May 17, 2017
Actual Study Completion Date :
May 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Panobinostat MTD + ICE

Phase 1: Escalating Panobinostat dose with routine ICE Chemotherapy

Drug: Panobinostat
Starting Day -6 of Cycle 1, 20 mg orally on Monday, Wednesday, and Friday during Cycles 1 and 2 (Days -6, -4, and -2 of Cycle 1 and Days 1, 3, 5, 8, 10, and 12 of Cycles 1 and 2); MTD found in Phase 1 used for same schedule in Phase 2.
Other Names:
  • LBH589B
  • Drug: Ifosfamide
    Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.
    Other Names:
  • Ifex
  • Drug: Mesna
    On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
    Other Names:
  • Mesnex
  • Drug: Carboplatin
    On Day 1 of Cycles 1-3, Standard Dose (Target area under curve (AUC) = 5mg/ml/min) by vein over 1 hour.
    Other Names:
  • Paraplatin
  • Drug: Etoposide
    On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
    Other Names:
  • VePesid
  • Experimental: ICE Chemotherapy

    Phase 2: Routine ICE Chemotherapy (Ifosfamide, Carboplatin, + Etoposide)

    Drug: Ifosfamide
    Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.
    Other Names:
  • Ifex
  • Drug: Mesna
    On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
    Other Names:
  • Mesnex
  • Drug: Carboplatin
    On Day 1 of Cycles 1-3, Standard Dose (Target area under curve (AUC) = 5mg/ml/min) by vein over 1 hour.
    Other Names:
  • Paraplatin
  • Drug: Etoposide
    On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
    Other Names:
  • VePesid
  • Drug: Pegfilgrastim
    Beginning Day 4 of Cycles 1-3, 6 mg under the skin.
    Other Names:
  • Neulasta
  • PEG-G-CSF
  • Experimental: Panobinostat + ICE

    Phase 2: Panobinostat with ICE Chemotherapy

    Drug: Panobinostat
    Starting Day -6 of Cycle 1, 20 mg orally on Monday, Wednesday, and Friday during Cycles 1 and 2 (Days -6, -4, and -2 of Cycle 1 and Days 1, 3, 5, 8, 10, and 12 of Cycles 1 and 2); MTD found in Phase 1 used for same schedule in Phase 2.
    Other Names:
  • LBH589B
  • Drug: Ifosfamide
    Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.
    Other Names:
  • Ifex
  • Drug: Mesna
    On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
    Other Names:
  • Mesnex
  • Drug: Carboplatin
    On Day 1 of Cycles 1-3, Standard Dose (Target area under curve (AUC) = 5mg/ml/min) by vein over 1 hour.
    Other Names:
  • Paraplatin
  • Drug: Etoposide
    On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
    Other Names:
  • VePesid
  • Drug: Pegfilgrastim
    Beginning Day 4 of Cycles 1-3, 6 mg under the skin.
    Other Names:
  • Neulasta
  • PEG-G-CSF
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Panobinostat + ICE [From first dose of panobinostat (or chemotherapy, in the arm of ICE alone) until 30 days after last dose, up to 6 years]

      Maximum Tolerated Dose (MTD) of Panobinostat + ICE

    2. Number of Participants With Complete Remission (CR) [Assessed after 3 cycles of ICE (2 months)]

      Will be assessed by Kaplan-Meier methods.

    Secondary Outcome Measures

    1. Percentage of Participants With Failure Free Survival (FFS) [16 months]

      FFS duration was calculated from date of study entry to date of progression or death or change of therapy, whichever came first.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Histologically confirmed classical Hodgkin lymphoma (nodular sclerosis, mixed cellularity, or lymphocyte-rich classical HL).

    2. Patients must have failed (relapsed or refractory) front-line standard anthracycline-containing regimen, such as ABVD, Stanford V, or BEACOPP.

    3. Bidimensionally measurable disease with at least 1 lesion >/= 2.0 cm in a single dimension

    4. Acceptable hematologic status:Hemoglobin >/= 9.0 g/dL, Absolute neutrophil count >/= 1500 cells/mm3, Platelet count >/= 100,000 cells/mm3

    5. Normal serum K+, Mg+, PO4, and total Ca++ (pre-treatment abnormal values may be therapeutically corrected before starting therapy and must be documented as normal or if abnormal values persist must be documented as clinically insignificant). Albumin should be >/= 3

    6. Pre-study World Health Organization (WHO) performance status of 0, 1, or 2

    7. Age >/= 16 years

    8. Voluntary signed Institutional Review Board (IRB) approved consent informed before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

    9. Patients of reproductive potential (female of child bearing potential has not been postmenopausal for at least 12 consecutive months or not surgically sterile; male of child bearing potential has not been surgically sterile)must follow accepted birth control methods (e.g. barrier method) during treatment.

    10. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

    11. Baseline Multiple Gated Acquisition (MUGA) or ECHO must demonstrate left ventricular ejection fraction (LVEF) >/= 50%.

    Exclusion Criteria:
    1. Lymphocyte predominant histology

    2. More than one prior chemotherapy regimens.

    3. Prior therapy with other HDAC inhibitors, including valproic acid

    4. Prior therapy with heat shock protein (HSP)-90 inhibitors

    5. Prior stem cell transplant

    6. Abnormal liver function: Bilirubin > 2.0 mg/dL (26 µmol/L), Alkaline phosphatase > 2 x upper limits of normal (ULN), aspartate aminotransferase AST (SGOT) and/or alanine aminotransferase ALT > 2 x ULN

    7. Serum creatinine >1.5 mg/dl

    8. Presence of Central Nervous System (CNS) involvement with Hodgkin lymphoma

    9. Presence of Human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS).

    10. Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer with a stable Prostate Specific Antigen PSA) for which the patient has not been disease free for at least 3 years.

    11. Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions which would compromise protocol objectives in the opinion of the investigator

    12. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:History or presence of sustained ventricular tachyarrhythmia, Any history of ventricular fibrillation or torsade de pointes, Bradycardia defined as HR< 50 bpm, Patients with pacemakers are eligible if HR >/= 50 bpm, Screening ECG with a corrected QT interval (QTc) > 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 Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

    13. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening, unless the female has recently (within 8 weeks) undergone egg harvest, which would result in the (Beta-hCG) test to be elevated without pregnancy. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

    14. Patient has received other investigational drugs within 14 days before enrollment or who have not recovered from side effects of those therapies.

    15. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

    16. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat

    17. Patients with diarrhea > Common Terminology Criteria for Adverse Events Version 4 (CTCAE V.4) grade 2

    18. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.

    19. Patients who have received either immunotherapy within </= 8 weeks; chemotherapy within </= 3 weeks; or radiation therapy to > 30% of marrow-bearing bone within </= 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.

    20. Patients who have undergone major surgery </= 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • Novartis

    Investigators

    • Principal Investigator: Yasuhiro Oki, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01169636
    Other Study ID Numbers:
    • 2010-0065
    • NCI-2012-01779
    First Posted:
    Jul 26, 2010
    Last Update Posted:
    Jan 6, 2021
    Last Verified:
    Dec 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by M.D. Anderson Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Recruitment period: January 2011 to March 2016
    Pre-assignment Detail 62 participants enrolled, 3 participants not treated on the study (1) adverse event (1) financial issue, and (1) consent withdrawal.
    Arm/Group Title Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat + ICE
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort.
    Period Title: Overall Study
    STARTED 3 6 20 13 14
    COMPLETED 3 6 17 12 11
    NOT COMPLETED 0 0 3 1 3

    Baseline Characteristics

    Arm/Group Title Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat + ICE Total
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Total of all reporting groups
    Overall Participants 3 6 20 12 11 52
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    100%
    6
    100%
    19
    95%
    12
    100%
    10
    90.9%
    50
    96.2%
    >=65 years
    0
    0%
    0
    0%
    1
    5%
    0
    0%
    1
    9.1%
    2
    3.8%
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    2
    33.3%
    9
    45%
    9
    75%
    7
    63.6%
    28
    53.8%
    Male
    2
    66.7%
    4
    66.7%
    11
    55%
    3
    25%
    4
    36.4%
    24
    46.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    16.7%
    5
    25%
    1
    8.3%
    1
    9.1%
    8
    15.4%
    White
    3
    100%
    5
    83.3%
    15
    75%
    11
    91.7%
    10
    90.9%
    44
    84.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    3
    100%
    6
    100%
    20
    100%
    12
    100%
    11
    100%
    52
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of Panobinostat + ICE
    Description Maximum Tolerated Dose (MTD) of Panobinostat + ICE
    Time Frame From first dose of panobinostat (or chemotherapy, in the arm of ICE alone) until 30 days after last dose, up to 6 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD)
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg
    Measure Participants 29
    Number [mg]
    30
    2. Primary Outcome
    Title Number of Participants With Complete Remission (CR)
    Description Will be assessed by Kaplan-Meier methods.
    Time Frame Assessed after 3 cycles of ICE (2 months)

    Outcome Measure Data

    Analysis Population Description
    Per protocol all Phase I Cohorts are analyzed as a single group.
    Arm/Group Title Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD) Phase II: Standard of Care (ICE) Phase II Panobinostat + ICE
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort.
    Measure Participants 29 12 11
    Complete Response
    21
    700%
    8
    133.3%
    9
    45%
    Partial Response
    4
    133.3%
    1
    16.7%
    0
    0%
    Stable Disease
    2
    66.7%
    2
    33.3%
    2
    10%
    Progressive Disease
    2
    66.7%
    1
    16.7%
    0
    0%
    3. Secondary Outcome
    Title Percentage of Participants With Failure Free Survival (FFS)
    Description FFS duration was calculated from date of study entry to date of progression or death or change of therapy, whichever came first.
    Time Frame 16 months

    Outcome Measure Data

    Analysis Population Description
    Per protocol all Phase I Cohorts are analyzed as a single group.
    Arm/Group Title Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD) Phase II: Standard of Care (ICE) Phase II Panobinostat + ICE
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1of ICE and during two weeks of C1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort.
    Measure Participants 29 12 11
    Number [percentage of participants]
    61
    2033.3%
    82
    1366.7%
    75
    375%

    Adverse Events

    Time Frame All AE were recorded from first dose of panobinostat (or chemotherapy, in the arm of ICE alone) until 30 days after last dose.
    Adverse Event Reporting Description
    Arm/Group Title Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat+ICE
    Arm/Group Description The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1 of ICE and during two weeks of C 1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1 of ICE and during two weeks of C 1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg The dose level for ICE is fixed. Patients received Panobinostat daily on Mon-Wed-Fri starting one week prior to cycle 1 of ICE and during two weeks of C 1-2 of ICE. Pre-defined dose levels of Panobinostat: Dose level -1 = 10 mg Dose level 0 = 20 mg: Dose level 1= 30 mg Patients are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort. Participants are randomized between ICE and Panobinostat plus ICE arms using A Bayesian adaptive algorithm. The dose level for Panobinostat was determined to be dose level 1 at 30mg as MTD during the phase I expansion cohort.
    All Cause Mortality
    Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat+ICE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/6 (0%) 0/20 (0%) 0/12 (0%) 0/11 (0%)
    Serious Adverse Events
    Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat+ICE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 1/6 (16.7%) 20/20 (100%) 12/12 (100%) 11/11 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 0/6 (0%) 11/20 (55%) 1/12 (8.3%) 0/11 (0%)
    Thrombocytopenia 0/3 (0%) 1/6 (16.7%) 19/20 (95%) 9/12 (75%) 11/11 (100%)
    Anemia 0/3 (0%) 0/6 (0%) 11/20 (55%) 6/12 (50%) 11/11 (100%)
    Cardiac disorders
    Syncope 0/3 (0%) 0/6 (0%) 1/20 (5%) 3/12 (25%) 0/11 (0%)
    Dizziness 0/3 (0%) 0/6 (0%) 0/20 (0%) 0/12 (0%) 1/11 (9.1%)
    Fatigue 0/3 (0%) 0/6 (0%) 0/20 (0%) 3/12 (25%) 4/11 (36.4%)
    Gastrointestinal disorders
    Vomiting 0/3 (0%) 0/6 (0%) 0/20 (0%) 0/12 (0%) 1/11 (9.1%)
    Diarrhea 0/3 (0%) 0/6 (0%) 0/20 (0%) 2/12 (16.7%) 0/11 (0%)
    Investigations
    Neutropenia 0/3 (0%) 0/6 (0%) 11/20 (55%) 3/12 (25%) 7/11 (63.6%)
    Metabolism and nutrition disorders
    Hyperbilirubinemia 0/3 (0%) 0/6 (0%) 1/20 (5%) 1/12 (8.3%) 0/11 (0%)
    Hypophosphatemia 0/3 (0%) 0/6 (0%) 1/20 (5%) 0/12 (0%) 0/11 (0%)
    Hyperglycemia 0/3 (0%) 0/6 (0%) 3/20 (15%) 0/12 (0%) 0/11 (0%)
    Hypomagnesemia 0/3 (0%) 0/6 (0%) 0/20 (0%) 0/12 (0%) 1/11 (9.1%)
    Hypokalemia 0/3 (0%) 0/6 (0%) 0/20 (0%) 0/12 (0%) 0/11 (0%)
    Other (Not Including Serious) Adverse Events
    Phase I: Panobinostat + ICE 10 mg Phase I: Panobinostat + ICE 20 mg Phase I: Panobinostat + ICE 30 mg Phase II: Standard of Care (ICE) Phase II: Panobinostat+ICE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 1/6 (16.7%) 19/20 (95%) 12/12 (100%) 11/11 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 0/6 (0%) 12/20 (60%) 1/12 (8.3%) 1/11 (9.1%)
    Anemia 0/3 (0%) 1/6 (16.7%) 19/20 (95%) 10/12 (83.3%) 11/11 (100%)
    Cardiac disorders
    Syncope 0/3 (0%) 0/6 (0%) 1/20 (5%) 3/12 (25%) 0/11 (0%)
    Dizziness 0/3 (0%) 0/6 (0%) 5/20 (25%) 1/12 (8.3%) 2/11 (18.2%)
    Fatigue 0/3 (0%) 1/6 (16.7%) 18/20 (90%) 12/12 (100%) 10/11 (90.9%)
    Dehydration 0/3 (0%) 0/6 (0%) 1/20 (5%) 2/12 (16.7%) 2/11 (18.2%)
    Atrial fibrillation 0/3 (0%) 0/6 (0%) 0/20 (0%) 2/12 (16.7%) 2/11 (18.2%)
    Gastrointestinal disorders
    Nausea 0/3 (0%) 1/6 (16.7%) 19/20 (95%) 12/12 (100%) 9/11 (81.8%)
    Constipation 0/3 (0%) 0/6 (0%) 3/20 (15%) 3/12 (25%) 0/11 (0%)
    Vomiting 0/3 (0%) 0/6 (0%) 11/20 (55%) 9/12 (75%) 7/11 (63.6%)
    Diarrhea 0/3 (0%) 0/6 (0%) 10/20 (50%) 3/12 (25%) 7/11 (63.6%)
    Mucositis 0/3 (0%) 0/6 (0%) 2/20 (10%) 2/12 (16.7%) 5/11 (45.5%)
    Investigations
    Neutropenia 0/3 (0%) 0/6 (0%) 19/20 (95%) 5/12 (41.7%) 8/11 (72.7%)
    Thrombocytopenia 0/3 (0%) 1/6 (16.7%) 19/20 (95%) 11/12 (91.7%) 11/11 (100%)
    AST 0/3 (0%) 1/6 (16.7%) 4/20 (20%) 1/12 (8.3%) 2/11 (18.2%)
    ALT 0/3 (0%) 1/6 (16.7%) 6/20 (30%) 1/12 (8.3%) 2/11 (18.2%)
    Metabolism and nutrition disorders
    Hyperbilirubinemia 0/3 (0%) 1/6 (16.7%) 1/20 (5%) 2/12 (16.7%) 1/11 (9.1%)
    Hypomagnesemia 0/3 (0%) 0/6 (0%) 6/20 (30%) 4/12 (33.3%) 5/11 (45.5%)
    Hypophosphatemia 0/3 (0%) 0/6 (0%) 1/20 (5%) 0/12 (0%) 0/11 (0%)
    Hypokalemia 0/3 (0%) 0/6 (0%) 6/20 (30%) 1/12 (8.3%) 2/11 (18.2%)
    Hyperglycemia 0/3 (0%) 1/6 (16.7%) 7/20 (35%) 5/12 (41.7%) 4/11 (36.4%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 1/6 (16.7%) 2/20 (10%) 1/12 (8.3%) 1/11 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Christopher Flowers, MD/ Chair, Chair, Lymphoma-Myeloma
    Organization UT MD Anderson Cancer Center
    Phone 713-745-6095
    Email crflowers@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01169636
    Other Study ID Numbers:
    • 2010-0065
    • NCI-2012-01779
    First Posted:
    Jul 26, 2010
    Last Update Posted:
    Jan 6, 2021
    Last Verified:
    Dec 1, 2020