A Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease

NCT01028313 | Withdrawn Phase 2

• 1 other identifier: SCRI BMT 02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone deacetylase (HDAC) inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting graft-versus-leukemia (GVL), may have a central role in the prevention and treatment of GVHD. This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.

Conditions

Chronic Graft-Versus-Host Disease

Keywords

Chronic Graft-Versus-Host Disease; GVHD; LBH589; Panobinostat

Outcome Measures

Primary Outcomes (1)

• To assess the response rate to panobinostat of patients with cGvHD inadequately treated with steroids and calcineurin inhibitors.

  30 months

Secondary Outcomes (5)

• To evaluate the safety and tolerability of panobinostat in patients with cGvHD.

  30 months

• To assess the steroid-sparing capacity of panobinostat (as proportion of patients able to discontinue steroids while receiving, or following therapy with, panobinostat).

  30 months

• To assess changes in quality of life (QOL) after treatment with panobinostat.

  30 months

• To analyze survival at 6 and 12 months after initiation of panobinostat.

  30 months

• To evaluate the relapse rate of the underlying malignancy as well as the occurrence of second malignancies at 6 and 12 months after initiation of panobinostat.

  30 months

Study Arms (1)

1

EXPERIMENTAL

Systemic Therapy

Drug: LBH589; Drug: Methylprednisolone

Interventions

LBH589 DRUG

20 mg PO three times weekly

Also known as: Panobinostat

1

Methylprednisolone DRUG

1 mg/kg/day PO continuously

Also known as: Medrol, Depo-Medrol

1

Eligibility Criteria

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

You may qualify if:

• Chronic GvHD following allogeneic HSCT of any source (bone marrow, peripheral blood, or cord blood stem cells), from any donor type (related, unrelated, or mismatched) and with any type of malignancy. Chronic GvHD will be defined according to NIH Consensus Criteria.
• Patients must have had inadequate response to treatment with steroids and calcineurin inhibitors. Patients must have been treated with an initial dose of at least 1 mg/kg/day of methylprednisolone (MP) or equivalent in combination with tacrolimus or cyclosporine and must fulfill the definition of steroid refractoriness or resistance. Steroid refractoriness or resistance will be defined as:
• Lack of any response after 1 month of treatment with MP, including 15 days of at least 0.5 mg/kg/day.
• Worsening of existing GvHD or new organ involvement at any time following one week of initiation of MP at 1 mg/kg/day.
• Reflare or worsening of GvHD at any time during steroid taper.
• Patients should not have received any drug or treatment for chronic GvHD other than steroids and calcineurin inhibitors (i.e., cyclosporine or tacrolimus).
• Patient must not have evidence of primary disease relapse.
• An ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
• Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥40%.
• No uncontrolled arrhythmias or symptoms of heart disease.
• FEV1, FVC, and DLCO ≥40%.
• Laboratory values as follows:
• white blood cell ≥2500/mm³;
• absolute neutrophil count (ANC) ≥1,000/mm³;
• hemoglobin ≥9.5 g%;

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
• Patients who will need valproic acid for any medical condition during the study or ≤5 days prior to first panobinostat treatment.
• Use of prior immunosuppressants other than steroids and calcineurin inhibitors(i.e. cyclosporine or tacrolimus).
• Chronic active hepatitis or cirrhosis.
• Impaired cardiac function including any of the following:
• Patients with congenital long QT syndrome;
• Patients with history or presence of sustained ventricular tachyarrhythmias;
• Patients with any history of ventricular fibrillation or Torsades de Pointes;
• Patients with bradycardia defined as HR \<50 bpm. Patients with pacemakers are eligible if HR ≥50 bpm.
• Patients with myocardial infarction or unstable angina ≤6 months prior to starting study drug;
• Right bundle branch block plus left anterior hemiblock (bifasicular block);
• Screening ECG with QTc \>450 msec;
• Congestive heart failure (CHF) \> New York Heart Association (NYHA) Class II (see Appendix D).
• Concomitant use of drugs with a risk of causing Torsades de Pointes (see Appendix A).
• Other concurrent severe and/or uncontrolled medical conditions.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (1)

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Panobinostat; Methylprednisolone; Methylprednisolone Acetate

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; 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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Daniel R Couriel, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 7, 2009
• First Posted: December 9, 2009
• Last Updated: February 13, 2013

Record last verified: 2013-02

Locations

US (1)