LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)

NCT01034657 | Terminated Phase 2 Results

• 3 other identifiers: CLBH589BDE04EudraCT 2009-010403-842009-010403-84
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

Brief Summary

This study assessed the efficacy and safety of LBH589 as single agent and in combination with ESA in red blood cell transfusion-dependent Low and Int-1 MDS patients being either refractory to ESA or with a low probability of response. The study had a non-randomized core phase followed by a randomized phase.

Conditions

Myelodysplastic Syndrome (MDS)

Keywords

MDS; bone marrow; anemia; cytopenia; transfusion dependance; EPO; ESA; erythropoietin; LBH589; Myelodysplastic Syndromes; hematopoietic improvement; IPSS Low; IPSS Int-1; HI-E; HDAC Inhibitor; HDAC-I; DAC-I; Deacetylase-Inhibitor; Histone Deacetylase-Inhibitor; red blood cell transfusions

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase

  HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, \<11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \< 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, \< 1.0 x 109/L): at least 100% increase and an absolute increase \> 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

  16 weeks

Secondary Outcomes (13)

• Percentage of Participants With HI-E - Randomized Phase

  32 weeks, 52 weeks

• Percentage of Participants With Objective Response During Core Phase

  16 weeks

• Percentage of Participants With Objective Response During the Randomized Phase

  32 weeks, 48 weeks

• Frequency Distribution of IPSS Score Status - Core Phase

  baseline

• Frequency Distribution of IPSS Score Status - Randomized Phase

  52 weeks

Study Arms (2)

LBH589

EXPERIMENTAL

During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.

Drug: LBH589

LBH589 + Epoetin Alfa

EXPERIMENTAL

During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.

Drug: LBH589; Drug: Epoetin Alfa

Interventions

LBH589 DRUG

LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.

Also known as: Panobinostat

LBH589; LBH589 + Epoetin Alfa

Epoetin Alfa DRUG

Epoetin alfa was supplied as 10000 IU/1 mL in a ready-to-use syringe.

Also known as: ESA, HEXAL®

LBH589 + Epoetin Alfa

Eligibility Criteria

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

You may qualify if:

• Patients with a lower risk MDS (LOW or INT-1 according to IPSS)
• Red blood cell transfusion dependency of at least 4 Units/8 weeks.
• Not responding to Erythropoietin stimulating agents (ESA) or having a low chance to do so
• Age-adjusted normal cardiac, kidney, liver function

You may not qualify if:

• Concomitant use of ESA
• Concomitant use of any other investigational drug
• Other malignancy that is not in remission for at least 1 year
• Platelet Count \< 75 x 109/L
• Impaired cardiac function or clinically significant cardiac diseases

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Bonn, 53105, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Duisburg, 47166, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia; Cytopenia

Interventions

Panobinostat; Epoetin Alfa

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic 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; Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: November 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 11, 2017
• Results First Posted: January 25, 2017

Record last verified: 2017-08

Locations

DE (12)