A Study of Galunisertib in Participants With Myelodysplastic Syndromes

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

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Placebo; Drug: Galunisertib

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • 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.
  • Düsseldorf, Germany, 40479
    • 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.
  • Jena, Germany, 07747
    • 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.
  • Lübeck, Germany, 23562
    • 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.
  • Ulm, Germany, 89081
    • 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.
  • Westerstede, Germany, 26655
    • 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.
• Italy
  • Firenze, Italy, 50134
    • 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.
  • Novara, Italy, 28100
    • 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.
  • Rome, Italy, 00161
    • 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.
• Spain
  • Barcelona, Spain, 08035
    • 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.
  • Madrid, Spain, 28050
    • 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.
  • Oviedo, Spain, 33011
    • 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.
  • Salamanca, Spain, 37007
    • 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.
  • Valencia, Spain, 46026
    • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase (ph) 2: Galunisertib + BSC; 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; Administered orally; Other Names: LY2157299
PLACEBO_COMPARATOR: Ph 3: Placebo + BSC; 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; Administered orally
EXPERIMENTAL: Ph 3: Galunisertib + BSC; 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; Administered orally; Other Names: LY2157299

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Follow up (final visit up to 24 months)
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.	Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days)
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.	Baseline through end of study treatment (24 weeks)
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.	Baseline through end of study treatment (24 weeks)
Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib	Population mean (between-participant coefficient variation [CV%]) apparent clearance.	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
Overall Survival (OS)	Overall survival is defined as the time from the date of first dose to the date of death from any cause.	Baseline to date of death from any cause (Up to 2 years)
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).	Baseline, Cycle 6 (Cycle = 28 days)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): September 1, 2017

Study Registration Dates

• First Submitted: December 6, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (ESTIMATE): December 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 11, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: 15242; H9H-MC-JBAV (OTHER: Eli Lilly and Company); 2013-003235-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR