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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01169636
First received: July 22, 2010
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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 pre-treatment and day 7±1 levels of serum Thymus and activation-regulated chemokine (TARC) and correlate the results with treatment response. ( TARC has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans.)
  • 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

Condition Intervention Phase
Hodgkin's Lymphoma
Drug: Panobinostat
Drug: Ifosfamide
Drug: Mesna
Drug: Carboplatin
Drug: Etoposide
Drug: Pegfilgrastim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Phase I Maximal Tolerated Dose (MTD) of Panobinostat + ICE [ Time Frame: Each cycle, 14 days from first dose of ICE ] [ Designated as safety issue: Yes ]
    MTD defined by patient dose limiting toxicities (DLT) at each dose level, monitored for 14 days (1 cycle) from first dose of ICE.


Secondary Outcome Measures:
  • Phase II Number of Patients with Complete Remission (CR) [ Time Frame: Assessed after 3 cycles of ICE (2 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 102
Study Start Date: January 2011
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panobinostat MTD + ICE
Phase 1: Escalating Panobinostat dose with routine ICE Chemotherapy
Drug: Panobinostat
Starting Day -6 of Cycle 1, 10 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 Name: LBH589B
Drug: Ifosfamide
Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.
Other Name: Ifex
Drug: Mesna
On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
Other Name: Mesnex
Drug: Carboplatin
On Day 1 of Cycles 1-3, Standard Dose (Target AUC = 5mg/ml/min) by vein over 1 hour.
Other Name: Paraplatin
Drug: Etoposide
On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
Other Name: 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 Name: Ifex
Drug: Mesna
On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
Other Name: Mesnex
Drug: Carboplatin
On Day 1 of Cycles 1-3, Standard Dose (Target AUC = 5mg/ml/min) by vein over 1 hour.
Other Name: Paraplatin
Drug: Etoposide
On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
Other Name: 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, 10 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 Name: LBH589B
Drug: Ifosfamide
Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.
Other Name: Ifex
Drug: Mesna
On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.
Other Name: Mesnex
Drug: Carboplatin
On Day 1 of Cycles 1-3, Standard Dose (Target AUC = 5mg/ml/min) by vein over 1 hour.
Other Name: Paraplatin
Drug: Etoposide
On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.
Other Name: VePesid
Drug: Pegfilgrastim
Beginning Day 4 of Cycles 1-3, 6 mg under the skin.
Other Names:
  • Neulasta
  • PEG-G-CSF

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 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., CHF NY 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. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01169636

Contacts
Contact: Yasuhiro Oki, MD 713-792-2860

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Yasuhiro Oki, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01169636     History of Changes
Other Study ID Numbers: 2010-0065, NCI-2012-01779
Study First Received: July 22, 2010
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chemotherapy
Panobinostat
Ifosfamide
Mesna
Etoposide
Carboplatin
Pegfilgrastim
ICE

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mesna
Etoposide
Etoposide phosphate
Isophosphamide mustard
Ifosfamide
Carboplatin
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014