Study of Efficacy and Safety of Eltrombopag in Patients With Poor Graft Function (ELTION)

• ClinicalTrials.gov Identifier: NCT03718533
• Recruitment Status: Completed
• First Posted: October 24, 2018
• Last Update Posted: January 12, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this phase II open-label, single-arm 36-week clinical trial is to evaluate the effect of eltrombopag in patients with poor graft function (PGF) after allogeneic-hematopoietic stem cells transplantation (allo-HSCT).

Condition or disease	Intervention/treatment	Phase
Poor Graft Function	Drug: Eltrombopag	Phase 2

Detailed Description:

The primary objective of this study is to evaluate the efficacy of eltrombopag for poor graft function on overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of eltrombopag.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The ELTION Study - A Multicenter Open-label Interventional Study of Eltrombopag in Patients With Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation
• Actual Study Start Date: December 17, 2018
• Actual Primary Completion Date: November 3, 2020
• Actual Study Completion Date: November 3, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eltrombopag; Patients will receive eltrombopag orally once daily up to 36 weeks.	Drug: Eltrombopag; 50mg Film-coated tablet and 25mg Film-coated tablet for oral use administration

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with hematologic response (partial and complete) [ Time Frame: Baseline up to approximately 16 weeks ]

   Evaluate the efficacy of eltrombopag on overall hematologic response (partial (PR) and complete (CR).

   A PR is defined when any of the following:

   • Platelet count ≥20,000/μL (with platelet transfusion independence), confirmed in two consecutive blood tests separated a minimum of 7 days.
   • Absolute neutrophil count (ANC) ≥1,000/μL (when pretreatment ANC was <1,000/μL), confirmed in two blood tests separated a minimum of 7 days.
   • Hemoglobin (Hb) ≥100g/L (when pretreatment Hb was <100g/L) (with Red Blood Cells transfusion independence), confirmed in two blood tests separated a minimum of 7 days.

   A CR is defined when all three of the following:

   • Platelet count ≥100,000/μL, confirmed in two blood tests separated a minimum of 7 days.
   • ANC ≥1,500/μL (when pretreatment ANC was <1,000/μL), confirmed in two blood tests separated a minimum of 7 days.
   • Hb ≥110 g/L (when pretreatment Hb was <100g/L), confirmed in two blood tests separated a minimum of 7 days.

Secondary Outcome Measures :

1. Percentage of patients who have a response in the neutrophil lineage [ Time Frame: Baseline up to approximately 16 weeks ]
   ANC ≥1,000/ µL or ≥ 1500/ µL in hematological results before week 16, confirmed in two consecutive blood tests separated a minimum of 7 days.
2. Percentage of patients who have a response in the platelet lineage [ Time Frame: Baseline up to approximately 16 weeks ]
   Platelet count ≥20,000/µL or ≥ 100000/µL in hematological results until week 16, confirmed in two consecutive blood tests separated a minimum of 7 days.
3. Percentage of patients who have a response in the hemoglobin lineage [ Time Frame: Baseline up to approximately 16 weeks ]
   Hb ≥100 g/L or ≥ 110 g/L in hematological results obtained before week 16, confirmed in two consecutive blood tests separated a minimum of 7 days
4. Percentage of participants that mantain hematologic response (partial and complete) [ Time Frame: Baseline up to approximately 24 and 36 weeks ]
   Evaluate if overall hematologic response (partial and complete) at week 16 is mantained at 24 and 36 weeks after treatment. Same values of 3 lineages separately (netrophil, platelet and hemoglobin) will be used to assess this endpoint.
5. Percentage of participants who were previously transfusion-dependent and do no longer require transfusions [ Time Frame: Baseline up to approximately 16 weeks and after week 16 to week 36 ]
   Patients previously transfusion-dependent who do no longer require platelets and/or RBC transfusion before and after the first 16 weeks of treatment.
6. Discontinuation of G-CSF and/or EPO therapy [ Time Frame: Baseline up to approximately 36 weeks ]
   Number of patients who discontinue or reduce by ≥50% the use of concomitant G-CSF and/or EPO therapy.
7. Overall survival [ Time Frame: Baseline up to approximately 36 weeks ]
   Time from the date of inclusion until the date of death due to any cause. All patients who discontinue from the study, regardless the reason of discontinuation, will be followed for survival for 24 and 36 weeks, unless they withdraw their consent, die or are lost-to follow-up, in which case will be censored at the last contact.
8. Percentage of participants surviving at 24 and 36 weeks [ Time Frame: Baseline up to approximately 24 and 36 weeks ]
   Percentage of patients still alive at 24 weeks and 36 weeks.
9. Duration of transfusion independence [ Time Frame: Baseline up to approximately 36 weeks ]
   Analyze the time period where patients did not receive any platelet or RBC transfusions

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must provide written, signed and dated informed consent form before any study assessment is performed
2. Male of female patients ≥ 18 years of age

3. Patients diagnosed with primary or secondary poor graft function (PGF) defined as two or more cytopenias after day +30 post-transplant (re-tested in a peripheral blood analysis at screening):

   1. Platelet count <20,000/ µL (mandatory)
   2. Absolute neutrophil count (ANC) <1,000/µL
   3. Hemoglobin <100 g/L
4. Presence of donor chimerism >90% in screening visit
5. Karnofsky status ≥90% (Karnofsky assessment must be performed within 7 days prior to Day 1)

Exclusion Criteria:

1. Pregnant or nursing (lactating women).
2. Evidence of active acute or chronic graft versus host disease (GVHD).
3. Evidence of any active malignancy.
4. Subjects who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive in screening visit.
5. Cytogenetic abnormality in chromosome 7 present before the allo-HSC.

6. Evidence of any clonal abnormality on cytogenetics (in bone marrow analysis).

   • A local post-transplant conventional cytogenetic assessment should be available within 8 weeks before Day 1.
   • If the cytogenetics is not valuable, i.e, it does not show metaphases, a FISH for MDS-related most frequent abnormalities including chromosome 7 is accepted.

   As a consequence, patients with dry tap bone marrow aspiration are NOT eligible.

7. Evidence of bone marrow involvement or progression of the underlying disease assessed by the applicable methods in each case.
8. Evidence of thrombotic microangiopathy.
9. Evidence of possible causes of cytopenia other than PGF (active infections, myelotoxic drugs, hypersplenism…).
10. Prior use of any thrombopoietin receptor (TPO-R) agonists for PGF.
11. AST or ALT levels >3 x ULN.
12. Creatinine level ≥1.5 x ULN.
13. Total bilirubin level ≥1.5 x ULN.
14. Previous thromboembolic event (other than line-related upper extremity thrombosis)
15. Hypersensitivity to eltrombopag or its components.

16. Clinically significant ECG abnormality history or current diagnosis of cardiac disease indicating significant risk of safety for subjects participating in the study such as uncontrolled or significant cardiac disease or impaired cardiac function including any of the following:

    1. . Corrected QTc > 450 msec (male subjects), > 460 msec (female subjects) using Fredericia correction (QTcF) on the screening ECG
    2. . Myocardial infarction
    3. . Uncontrolled congestive heart failure
    4. . Unstable angina
    5. . Congenital long QT syndrome.
17. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
18. Patient with liver cirrhosis.
19. Risk factors for Torsade de Pointes including uncorrected hypokalemia or hypomagnesemia.
20. Subjects with any serious and/ or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with patient´s safety, obtaining informed consent or compliance with the study procedures as per investigator discretion.

Contacts and Locations

Locations

Spain

Novartis Investigative Site

Malaga, Andalucia, Spain, 29010

Novartis Investigative Site

Salamanca, Castilla Y Leon, Spain, 37007

Novartis Investigative Site

Valencia, Comunidad Valenciana, Spain, 46010

Novartis Investigative Site

Palma De Mallorca, Islas Baleares, Spain, 07120

Novartis Investigative Site

San Sebastian, Pais Vasco, Spain, 20080

Novartis Investigative Site

Vigo, Pontevedra, Spain, 36212

Novartis Investigative Site

Barcelona, Spain, 08041

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03718533
• Other Study ID Numbers: CETB115EES03; 2018-001129-15 ( EudraCT Number )
• First Posted: October 24, 2018
• Last Update Posted: January 12, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Eltrombopag, hematological response; poor graft function, stem cell transplantation. CETB115EES03, adult, ELTION, phase II