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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01034657
Other study ID # CLBH589BDE04
Secondary ID EudraCT 2009-010
Status Terminated
Phase Phase 2
First received December 16, 2009
Last updated August 8, 2017
Start date November 2009
Est. completion date August 2012

Study information

Verified date August 2017
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 34
Est. completion date August 2012
Est. primary completion date August 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
LBH589
LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.
Epoetin Alfa
Epoetin alfa was supplied as 10000 IU/1 mL in a ready-to-use syringe.

Locations

Country Name City State
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Bonn
Germany Novartis Investigative Site Dresden
Germany Novartis Investigative Site Duesseldorf
Germany Novartis Investigative Site Duisburg
Germany Novartis Investigative Site Frankfurt
Germany Novartis Investigative Site Goettingen
Germany Novartis Investigative Site Hannover
Germany Novartis Investigative Site Leipzig
Germany Novartis Investigative Site Mannheim Baden-Württemberg
Germany Novartis Investigative Site Muenchen
Germany Novartis Investigative Site Ulm

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Percentage of Participants With HI-E - Randomized 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. 32 weeks, 52 weeks
Secondary Percentage of Participants With Objective Response During Core Phase 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. 16 weeks
Secondary Percentage of Participants With Objective Response During the Randomized Phase 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. 32 weeks, 48 weeks
Secondary Frequency Distribution of IPSS Score Status - Core Phase 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). baseline
Secondary Frequency Distribution of IPSS Score Status - Randomized Phase 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). 52 weeks
Secondary Mean Single Scoring Values of the IPSS - Core Phase 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). baseline
Secondary Mean Single Scoring Values of the IPSS - Randomized Phase 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). 52 weeks
Secondary Overall Survival (OS) - Overall Period OS was defined as the time from start of treatment to death from any cause. 48 weeks
Secondary Time to Response - Overall Period 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. 52 weeks
Secondary Event-free Survival (EFS) - Overall Period EFS was defined as the time from start of treatment to failure or death from any cause. 52 weeks
Secondary Progression-free Survival (PFS) - Overall Period PFS was defined as the time from start of treatment to disease progression or death from MDS. 52 weeks
Secondary Disease-free Survival (DFS) - Overall Period DFS was defined as the time from start of treatment to the time to relapse. 52 weeks
Secondary Time to Cause-specific Death - Overall Period Time to cause-specific death was defined as the time from start of treatment to death related to MDS. 52 weeks
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