Brief Summary

The purpose of this study is to investigate the effect of the study drug known as galunisertib in participants with myelodysplastic syndromes (MDS). Participants with different degrees of disease (very low, low, and intermediate risk) will be studied. The study treatment is expected to last about 6 months for each participant.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Mar 2014

Typical duration for phase_2

Geographic Reach

3 countries

14 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.5 years study duration

First Submitted

Initial submission to the registry

December 6, 2013

Completed

5 days until next milestone

First Posted

Study publicly available on registry

December 11, 2013

Completed

3 months until next milestone

Study Start

First participant enrolled

March 1, 2014

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed

1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed

1.5 years until next milestone

Results Posted

Study results publicly available

March 7, 2019

Completed

Last Updated

September 11, 2019

Status Verified

August 1, 2019

Enrollment Period

2 years

First QC Date

December 6, 2013

Results QC Date

September 21, 2018

Last Update Submit

August 28, 2019

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

Percentage of Participants With Hematological Improvement (HI)
Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days).
Baseline through end of study treatment (24 weeks)
Percentage of Participants Who Are Transfusion-free or Have Hemoglobin (Hb) Increase ≥1.5 Grams/Deciliter Maintained for 8 Weeks During Phase 3
Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved.
Baseline through end of study treatment (24 weeks)

Secondary Outcomes (7)

Change From Baseline in Brief Fatigue Inventory (BFI)
Baseline, Follow up (final visit up to 24 months)
Change From Baseline in EuroQol 5-Dimension 5 Level Instrument
Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days)
Percentage of Participants With Cytogenetic Response
Baseline through end of study treatment (24 weeks)
Percentage of Participants Who Are Hospitalized (Resource Utilization)
Baseline through end of study treatment (24 weeks)
Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib
Day 1 pre-dose & between 0.5 to 2 hours post dose; Day 14 pre-dose, between 0.5 to 2 & between 3 to 5 hours post dose; Days 15 & 16 (if logistically possible) between 0.5 to 2 hours post dose
+2 more secondary outcomes

Study Arms (3)

Phase (ph) 2: Galunisertib + BSC

EXPERIMENTAL

Ph 2. 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit.

Drug: Galunisertib

Ph 3: Placebo + BSC

PLACEBO COMPARATOR

Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive BSC according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm.

Drug: Placebo

Ph 3: Galunisertib + BSC

EXPERIMENTAL

150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm.

Drug: Galunisertib

Interventions

GalunisertibDRUG

Administered orally

Also known as: LY2157299

Ph 3: Galunisertib + BSCPhase (ph) 2: Galunisertib + BSC

PlaceboDRUG

Administered orally

Ph 3: Placebo + BSC

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Confirmed diagnosis of MDS based on the World Health Organization (WHO) criteria
Participants with 5q deletions are allowed only if they have failed or are intolerant of lenalidomide treatment
Participants must have a Revised International Prognostic Scoring System (IPSS-R) category of very low-, low-, or intermediate-risk disease
In the 8 weeks prior to registration, participants in phase 2 should have anemia with Hb ≤10.0 g/dL (based on the average of 2 baseline measurements and untransfused for at least 1 week) with or without red blood cell (RBC) transfusion dependence confirmed for a minimum of 8 weeks before enrollment
For phase 3, participants should have anemia with RBC transfusion dependence confirmed within 8 weeks before enrollment
Performance status ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale

You may not qualify if:

No history of moderate or severe cardiac disease
No prior history of acute myeloid leukemia (AML)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Eli Lilly and Companylead

Study Sites (14)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Dresden, 01307, Germany

Location

Düsseldorf, 40479, Germany

Location

Jena, 07747, Germany

Location

Lübeck, 23562, Germany

Location

Ulm, 89081, Germany

Location

Westerstede, 26655, Germany

Location

Florence, 50134, Italy

Location

Novara, 28100, Italy

Location

Rome, 00161, Italy

Location

Barcelona, 08035, Spain

Location

Madrid, 28050, Spain

Location

Oviedo, 33011, Spain

Location

Salamanca, 37007, Spain

Location

Valencia, 46026, Spain

Location

Related Publications (1)

Santini V, Valcarcel D, Platzbecker U, Komrokji RS, Cleverly AL, Lahn MM, Janssen J, Zhao Y, Chiang A, Giagounidis A, Guba SC, Gueorguieva I, Girvan AC, da Silva Ferreira M, Bhagat TD, Pradhan K, Steidl U, Sridharan A, Will B, Verma A. Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes. Clin Cancer Res. 2019 Dec 1;25(23):6976-6985. doi: 10.1158/1078-0432.CCR-19-1338. Epub 2019 Sep 3.
PMID: 31481511DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

LY-2157299

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Limitations and Caveats

The response rate at interim analysis did not meet the predefined rate. The Phase 3 portion was not initiated and the sponsor decided on early discontinuation of the study at the conclusion of Phase 2.

Results Point of Contact

Title: Chief Medical Officer
Organization: Eli Lilly and Company

Study Officials

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee: No
Restriction Type: GT60
Restrictive Agreement: Yes

Study Design

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

Study Record Dates

First Submitted

December 6, 2013

First Posted

December 11, 2013

Study Start

March 1, 2014

Primary Completion

March 1, 2016

Study Completion

September 1, 2017

Last Updated

September 11, 2019

Results First Posted

March 7, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing: Will share
Shared Documents: STUDY PROTOCOL, SAP, CSR
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

DE(6)ES(5)IT(3)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Results Posted

Conditions

Outcome Measures

Primary Outcomes (2)

Secondary Outcomes (7)

Study Arms (3)

Phase (ph) 2: Galunisertib + BSC

Ph 3: Placebo + BSC

Ph 3: Galunisertib + BSC

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (14)

Related Publications (1)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Limitations and Caveats

Results Point of Contact

Study Officials

Publication Agreements

Study Design

Study Record Dates

Data Sharing

Locations