This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been terminated.
(The study was terminated due to lack of efficacy of single agent LBH589 in the 4 month open label core phase and due to enrollment difficulties.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01034657
First received: December 16, 2009
Last updated: November 30, 2016
Last verified: November 2016
December 16, 2009
November 30, 2016
November 2009
August 2012   (Final data collection date for primary outcome measure)
Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase [ Time Frame: 16 weeks ]
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.
Evaluation of the hematological improvement of the erythropoietic system (HI-E) using modified IWG criteria (Cheson 2006) in patients treated with LBH589 single agent [ Time Frame: 16 weeks ]
Complete list of historical versions of study NCT01034657 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With HI-E - Randomized Phase [ Time Frame: 32 weeks, 52 weeks ]
    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.
  • Percentage of Participants With Objective Response During Core Phase [ Time Frame: 16 weeks ]
    Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (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%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.
  • Percentage of Participants With Objective Response During the Randomized Phase [ Time Frame: 32 weeks, 48 weeks ]
    Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (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%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.
  • Frequency Distribution of IPSS Score Status - Core Phase [ Time Frame: baseline ]
    The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
  • Frequency Distribution of IPSS Score Status - Randomized Phase [ Time Frame: 52 weeks ]
    The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
  • Mean Single Scoring Values of the IPSS - Core Phase [ Time Frame: baseline ]
    The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
  • Mean Single Scoring Values of the IPSS - Randomized Phase [ Time Frame: 52 weeks ]
    The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
  • Overall Survival (OS) - Overall Period [ Time Frame: 48 weeks ]
    OS was defined as the time from start of treatment to death from any cause.
  • Time to Response - Overall Period [ Time Frame: 52 weeks ]
    Time to response was defined as the time from start of treatment to the first documented response (complete [CR] or partial [PR]) according to modified IWG criteria for HI.
  • Event-free Survival (EFS) - Overall Period [ Time Frame: 52 weeks ]
    EFS was defined as the time from start of treatment to failure or death from any cause.
  • Progression-free Survival (PFS) - Overall Period [ Time Frame: 52 weeks ]
    PFS was defined as the time from start of treatment to disease progression or death from MDS.
  • Disease-free Survival (DFS) - Overall Period [ Time Frame: 52 weeks ]
    DFS was defined as the time from start of treatment to the time to relapse.
  • Time to Cause-specific Death - Overall Period [ Time Frame: 52 weeks ]
    Time to cause-specific death was defined as the time from start of treatment to death related to MDS.
  • Comparison of the hematological improvement of the erythropoietic system (HI-E) using modified IWG criteria (Cheson 2006) in patients treated with either LBH589 single agent or with LBH589 and ESA combination treatment. [ Time Frame: up to 48 weeks ]
  • Evaluation of the objective response rate (CR + PR and HI-P and HI-N) according to modified IWG criteria (Cheson et al.). [ Time Frame: up to 48 weeks ]
  • Determination of the IPSS status as well as the single scoring values of the IPSS for patients at baseline and EOS (end of study). [ Time Frame: up to 48 weeks ]
  • Determination of the time to response, event-free survival, progression-free survival (PFS), disease-free survival (DFS), time to cause-specific death, and overall survival (OS) in this patient population. [ Time Frame: up to 48 weeks ]
  • Evaluation of the safety and tolerability profile of LBH589 and LBH589 + ESA in low and INT-1 risk MDS patients [ Time Frame: up to 48 weeks ]
Not Provided
Not Provided
 
LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)
A One Year, Open Label, Multicenter Trial of LBH589 Alone or 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 GErman PAnobinostat Low Risk MDS Trial - GEPARD Study
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Myelodysplastic Syndrome (MDS)
  • Drug: LBH589
    LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.
    Other Name: Panobinostat
  • Drug: Epoetin Alfa
    Epoetin alfa was supplied as 10000 IU/1 mL in a ready-to-use syringe.
    Other Name: ESA, HEXAL®
  • Experimental: LBH589
    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.
    Intervention: Drug: LBH589
  • Experimental: LBH589 + Epoetin Alfa
    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.
    Interventions:
    • Drug: LBH589
    • Drug: Epoetin Alfa
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
34
August 2012
August 2012   (Final data collection date for primary outcome measure)

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
 
NCT01034657
CLBH589BDE04
EudraCT 2009-010403-84 ( Registry Identifier: EudraCT )
2009-010403-84
Not Provided
Not Provided
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP