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

NCT01169636 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2010-0065NCI-2012-01779
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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

Conditions

Hodgkin's Lymphoma

Keywords

Chemotherapy; Panobinostat; Ifosfamide; Mesna; Etoposide; Carboplatin; Pegfilgrastim; ICE

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Panobinostat + ICE

  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

• Number of Participants With Complete Remission (CR)

  Will be assessed by Kaplan-Meier methods.

  Assessed after 3 cycles of ICE (2 months)

Secondary Outcomes (1)

• Percentage of Participants With Failure Free Survival (FFS)

  16 months

Study Arms (3)

Panobinostat MTD + ICE

EXPERIMENTAL

Phase 1: Escalating Panobinostat dose with routine ICE Chemotherapy

Drug: Panobinostat; Drug: Ifosfamide; Drug: Mesna; Drug: Carboplatin; Drug: Etoposide

ICE Chemotherapy

EXPERIMENTAL

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

Drug: Ifosfamide; Drug: Mesna; Drug: Carboplatin; Drug: Etoposide; Drug: Pegfilgrastim

Panobinostat + ICE

EXPERIMENTAL

Phase 2: Panobinostat with ICE Chemotherapy

Drug: Panobinostat; Drug: Ifosfamide; Drug: Mesna; Drug: Carboplatin; Drug: Etoposide; Drug: Pegfilgrastim

Interventions

Panobinostat DRUG

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.

Also known as: LBH589B

Panobinostat + ICE; Panobinostat MTD + ICE

Ifosfamide DRUG

Day 1 of Cycles 1-3, 5 grams/m2 by vein over 24 hours.

Also known as: Ifex

ICE Chemotherapy; Panobinostat + ICE; Panobinostat MTD + ICE

Mesna DRUG

On Day 1 of Cycles 1-3, 2 grams/m2 by vein over 12 hours.

Also known as: Mesnex

ICE Chemotherapy; Panobinostat + ICE; Panobinostat MTD + ICE

Carboplatin DRUG

On Day 1 of Cycles 1-3, Standard Dose (Target area under curve (AUC) = 5mg/ml/min) by vein over 1 hour.

Also known as: Paraplatin

ICE Chemotherapy; Panobinostat + ICE; Panobinostat MTD + ICE

Etoposide DRUG

On Days 1-3 of Cycles 1-3, 100 mg/m2 by vein over 2 hours.

Also known as: VePesid

ICE Chemotherapy; Panobinostat + ICE; Panobinostat MTD + ICE

Pegfilgrastim DRUG

Beginning Day 4 of Cycles 1-3, 6 mg under the skin.

Also known as: Neulasta, PEG-G-CSF

ICE Chemotherapy; Panobinostat + ICE

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed classical Hodgkin lymphoma (nodular sclerosis, mixed cellularity, or lymphocyte-rich classical HL).
• Patients must have failed (relapsed or refractory) front-line standard anthracycline-containing regimen, such as ABVD, Stanford V, or BEACOPP.
• Bidimensionally measurable disease with at least 1 lesion \>/= 2.0 cm in a single dimension
• Acceptable hematologic status:Hemoglobin \>/= 9.0 g/dL, Absolute neutrophil count \>/= 1500 cells/mm3, Platelet count \>/= 100,000 cells/mm3
• 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
• Pre-study World Health Organization (WHO) performance status of 0, 1, or 2
• Age \>/= 16 years
• 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.
• 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.
• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
• Baseline Multiple Gated Acquisition (MUGA) or ECHO must demonstrate left ventricular ejection fraction (LVEF) \>/= 50%.

You may not qualify if:

• Lymphocyte predominant histology
• More than one prior chemotherapy regimens.
• Prior therapy with other HDAC inhibitors, including valproic acid
• Prior therapy with heat shock protein (HSP)-90 inhibitors
• Prior stem cell transplant
• 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
• Serum creatinine \>1.5 mg/dl
• Presence of Central Nervous System (CNS) involvement with Hodgkin lymphoma
• Presence of Human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS).
• 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.
• 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
• 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)
• 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.
• Patient has received other investigational drugs within 14 days before enrollment or who have not recovered from side effects of those therapies.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Panobinostat; Ifosfamide; Mesna; Carboplatin; Etoposide; pegfilgrastim; pegylated granulocyte colony-stimulating factor, human

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Dr. Christopher Flowers, MD/ Chair, Chair, Lymphoma-Myeloma
• Organization: UT MD Anderson Cancer Center

crflowers@mdanderson.org

713-745-6095

Study Officials

• Yasuhiro Oki, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 26, 2010
• Study Start: January 31, 2011
• Primary Completion: May 17, 2017
• Study Completion: May 17, 2017
• Last Updated: January 6, 2021
• Results First Posted: January 6, 2021

Record last verified: 2020-12

Locations

US (1)