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

NCT03718533 | Terminated Phase 2 Results

• 2 other identifiers: CETB115EES032018-001129-15
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study was to evaluate the efficacy of eltrombopag for poor graft function (PGF) on overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of eltrombopag in patients with poor graft function after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Conditions

Poor Graft Function

Keywords

Eltrombopag; Hematological response; Poor graft function; Stem cell transplantation; Adult; ELTION; Phase II

Outcome Measures

Primary Outcomes (1)

• Hematologic Response Rate by 16 Weeks After the Initiation of Eltrombopag

  Hematologic response rate was defined as the percentage of participants who met the criteria of either complete response (CR) or partial response (PR) by Week 16. PR was defined when any of the following: Platelet count ≥ 20000/microliter(μL) (with platelet transfusion independence), absolute neutrophil count (ANC) ≥1000/μL (when pretreatment ANC was \<1000/μL) and/or hemoglobin (Hb) ≥100 gram(g)/ liter(L) (when pretreatment Hb was \<100g/L) (with red blood cells transfusion independence), confirmed in two blood tests separated a minimum of 7 days. CR was defined when all of the following: platelet count ≥100000/μL, ANC ≥1500/μL (when pretreatment ANC was \<1000/μL) and Hb ≥110 g/L (when pretreatment Hb was \<100g/L), confirmed in two blood tests separated a minimum of 7 days. Participants who discontinued before Week 16 were considered as responders if, in the last evaluation, they had PR or CR. The 95% Confidence Interval (CI) was the binomial exact CI based on Clopper-Pearson method.

  Baseline up to Week 16

Secondary Outcomes (11)

• Percentage of Participants Who Had a Response in the Neutrophil Lineage

  Week 16, 20, 24, 30 and 36

• Percentage of Participants Who Had a Response in the Platelet Lineage

  Week 16, 20, 24, 30 and 36

• Percentage of Participants Who Had a Response in the Hemoglobin Lineage

  Week 16, 20, 24, 30 and 36

• Hematologic Response Rate at Week 24 and 36

  Week 24 and 36

• Percentage of Participants Who Were Previously Platelet Transfusion-dependent and Did no Longer Require Platelet Transfusions After the Initiation of Eltrombopag

  From start of treatment to end of treatment, assessed up to 36 weeks

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Patients received eltrombopag orally once daily up to 36 weeks.

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag was provided as 50 mg or 25 mg film-coated tablets for oral use administration

Eltrombopag

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Male of female patients ≥ 18 years of age
• 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):
• Platelet count \<20,000/ µL (mandatory)
• Absolute neutrophil count (ANC) \<1,000/µL
• Hemoglobin \<100 g/L
• Presence of donor chimerism \>90% in screening visit
• Karnofsky status ≥90% (Karnofsky assessment must be performed within 7 days prior to Day 1)

You may not qualify if:

• Pregnant or nursing (lactating women).
• Evidence of active acute or chronic graft versus host disease (GVHD).
• Evidence of any active malignancy.
• Subjects who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive in screening visit.
• Cytogenetic abnormality in chromosome 7 present before the allo-HSC.
• 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.
• Evidence of bone marrow involvement or progression of the underlying disease assessed by the applicable methods in each case.
• Evidence of thrombotic microangiopathy.
• Evidence of possible causes of cytopenia other than PGF (active infections, myelotoxic drugs, hypersplenism…).
• Prior use of any thrombopoietin receptor (TPO-R) agonists for PGF.
• AST or ALT levels \>3 x ULN.
• Creatinine level ≥1.5 x ULN.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, 20080, Spain

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Vigo, Pontevedra, 36212, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Related Links

• Plain Language Trial Summary

MeSH Terms

Interventions

eltrombopag

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 24, 2018
• Study Start: December 17, 2018
• Primary Completion: November 3, 2020
• Study Completion: November 3, 2020
• Last Updated: February 29, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (7)