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A Study of Galunisertib in Participants With Myelodysplastic Syndromes

Primary Purpose

Myelodysplastic Syndromes

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Galunisertib

Placebo

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Phase (ph) 2: Galunisertib + BSC

Ph 3: Placebo + BSC

Ph 3: Galunisertib + BSC

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

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.

Secondary Outcome Measures

Change From Baseline in Brief Fatigue Inventory (BFI)

The Brief Fatigue Inventory (BFI) is a brief participant-reported questionnaire that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity of fatigue is assessed using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine.

Change From Baseline in EuroQol 5-Dimension 5 Level Instrument

EuroQol 5-Dimension 5 Level Instrument (EQ-5D-5L) was not conducted, trial terminated prior to Phase 3. No data collected.

Percentage of Participants With Cytogenetic Response

Percentage of Participants with Cytogenetic Response with either complete or partial response. Complete cytogenetic response is the disappearance of the chromosomal abnormality without appearance of new ones. Partial cytogenetic response is at least 50% reduction of the chromosomal abnormality.

Percentage of Participants Who Are Hospitalized (Resource Utilization)

Percentage of any participant with a hospitalization admission and discharge date on the same day are counted as a half-day in the duration of hospitalization.

Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib

Population mean (between-participant coefficient variation [CV%]) apparent clearance.

Overall Survival (OS)

Overall survival is defined as the time from the date of first dose to the date of death from any cause.

Number of Participants With a Change in Bone Marrow Fibrosis Grading

Change from baseline in bone marrow fibrosis measured the number of participants with a change in bone marrow fibrosis grading (negative, mild, moderate, and severe).

Full Information

NCT ID

NCT02008318

First Posted

December 6, 2013

Last Updated

August 28, 2019

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02008318

Brief Title

A Study of Galunisertib in Participants With Myelodysplastic Syndromes

Official Title

Phase 2/3 Study of Monotherapy LY2157299 Monohydrate in Very Low-, Low-, and Intermediate-Risk Patients With Myelodysplastic Syndromes

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

March 2014 (undefined)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase (ph) 2: Galunisertib + BSC

Arm Type

Experimental

Arm Description

Arm Title

Ph 3: Placebo + BSC

Arm Type

Placebo Comparator

Arm Description

Arm Title

Ph 3: Galunisertib + BSC

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Galunisertib

Other Intervention Name(s)

LY2157299

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Percentage of Participants With Hematological Improvement (HI)

Description

Time Frame

Baseline through end of study treatment (24 weeks)

Title

Percentage of Participants Who Are Transfusion-free or Have Hemoglobin (Hb) Increase ≥1.5 Grams/Deciliter Maintained for 8 Weeks During Phase 3

Description

Time Frame

Baseline through end of study treatment (24 weeks)

Secondary Outcome Measure Information:

Title

Change From Baseline in Brief Fatigue Inventory (BFI)

Description

Time Frame

Baseline, Follow up (final visit up to 24 months)

Title

Change From Baseline in EuroQol 5-Dimension 5 Level Instrument

Description

EuroQol 5-Dimension 5 Level Instrument (EQ-5D-5L) was not conducted, trial terminated prior to Phase 3. No data collected.

Time Frame

Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days)

Title

Percentage of Participants With Cytogenetic Response

Description

Time Frame

Baseline through end of study treatment (24 weeks)

Title

Percentage of Participants Who Are Hospitalized (Resource Utilization)

Description

Percentage of any participant with a hospitalization admission and discharge date on the same day are counted as a half-day in the duration of hospitalization.

Time Frame

Baseline through end of study treatment (24 weeks)

Title

Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib

Description

Population mean (between-participant coefficient variation [CV%]) apparent clearance.

Time Frame

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

Title

Overall Survival (OS)

Description

Overall survival is defined as the time from the date of first dose to the date of death from any cause.

Time Frame

Baseline to date of death from any cause (Up to 2 years)

Title

Number of Participants With a Change in Bone Marrow Fibrosis Grading

Description

Change from baseline in bone marrow fibrosis measured the number of participants with a change in bone marrow fibrosis grading (negative, mild, moderate, and severe).

Time Frame

Baseline, Cycle 6 (Cycle = 28 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: No history of moderate or severe cardiac disease No prior history of acute myeloid leukemia (AML)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

City

Düsseldorf

ZIP/Postal Code

40479

Country

Germany

Facility Name

City

Jena

ZIP/Postal Code

07747

Country

Germany

Facility Name

City

Lübeck

ZIP/Postal Code

23562

Country

Germany

Facility Name

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

City

Westerstede

ZIP/Postal Code

26655

Country

Germany

Facility Name

City

Firenze

ZIP/Postal Code

50134

Country

Italy

Facility Name

City

Novara

ZIP/Postal Code

28100

Country

Italy

Facility Name

City

Rome

ZIP/Postal Code

00161

Country

Italy

Facility Name

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28050

Country

Spain

Facility Name

City

Oviedo

ZIP/Postal Code

33011

Country

Spain

Facility Name

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

City

Valencia

ZIP/Postal Code

46026

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing 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.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Citations:

PubMed Identifier

31481511

Citation

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.

Results Reference

derived

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A Study of Galunisertib in Participants With Myelodysplastic Syndromes

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