A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
3 other identifiers
interventional
36
5 countries
22
Brief Summary
The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with dexamethasone in participants with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma (T-ALL/T-LBL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2015
Typical duration for phase_1
22 active sites
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
First Submitted
Initial submission to the registry
August 5, 2015
CompletedFirst Posted
Study publicly available on registry
August 7, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 15, 2018
CompletedResults Posted
Study results publicly available
February 6, 2019
CompletedSeptember 11, 2019
August 1, 2019
2.3 years
August 5, 2015
January 14, 2019
August 28, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria: CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of the patient from the study during Cycle 1).
Cycle 1 (Up To 28 Days)
Recommended Dose of LY3039478 in Combination With Dexamethasone
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria:CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting.A dose-limiting equivalent toxicity (DLET) was defined as an AE occurring between Day 1 and Day 28 of any cycle (other than Cycle 1) for a patient enrolled in the Phase 1 portion or in any cycle (including Cycle 1) for a patient enrolled in the Phase 2 portion that would have met the criteria for DLT if it had occurred during Cycle 1 for a patient enrolled in the Phase 1 portion.
Cycle 1 (28 Days)
Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR)
ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of patients achieving a CR or a CRi divided by the total number of patients randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.
Baseline to Objective Disease Progression (Up To 2 Months)
Secondary Outcomes (10)
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1
Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8
Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours
Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations
Baseline to Objective Disease Progression (Up To 12 Months)
Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR
Baseline to Objective Disease Progression (Up To 12 Months)
Phase 2: Number of Participants Who Achieve PR
Baseline to Objective Disease Progression (Up To 12 Months)
- +5 more secondary outcomes
Study Arms (4)
LY3039478 + Dexamethasone (Adult)
EXPERIMENTALPart A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.
LY3039478 + Dexamethasone (Pediatric)
EXPERIMENTALPart B: LY3039478 administered orally TIW at escalating doses and dexamethasone administered orally twice a day (BID) on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Part B of the study.
Phase 2: LY3039478 + Dexamethasone
EXPERIMENTALLY3039478 administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study.
Phase 2: Placebo + Dexamethasone
PLACEBO COMPARATORPlacebo administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study.
Interventions
Administered orally
Administered orally
Eligibility Criteria
You may qualify if:
- Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
- T-ALL or T-LBL participants with relapsed/refractory disease.
- Have had at least 60 days between prior hematopoietic stem cell transplantation (SCT) and first dose of study drug.
- Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale for adults.
- Lansky score \>50% for participants \<16 years old.
- Have adequate organ function.
- Are at least:
- adult Phase 1 Part A and Phase 2: ≥16 years old at the time of screening
- pediatric Phase 1 Part B: 2 to \<16 years old
- Men and women with reproductive potential: Must agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug(s) or country requirements, whichever is longer.
- Females with childbearing potential: Have had a negative serum pregnancy test ≤7 days before the first dose of study drug and also must not be breastfeeding.
- Are able to swallow capsules and tablets.
You may not qualify if:
- Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.
- Have evidence of uncontrolled, active infection \<7 days prior to administration of study medication.
- Have current or recent gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.
- Have active leukemic involvement of the central nervous system (CNS).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
City of Hope National Medical Center
Duarte, California, 91010-0269, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19106, United States
University of Texas MD Anderson
Houston, Texas, 77030, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Lille, 59037, France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Nantes, 44093, France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Paris, 75475, France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Pierre-Bénite, 69495, France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Toulouse, 31059, France
Johann Wolfgang Goethe-Universität Frankfurt
Frankfurt, 60590, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Ulm, 89081, Germany
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.
Haifa, 3525408, Israel
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.
Jerusalem, 9112001, Israel
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.
Ramat Gan, 5266202, Israel
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.
Tel Aviv, 6423906, Israel
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Milan, 20132, Italy
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Napoli, 80131, Italy
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Torino, 10126, Italy
Related Publications (1)
Borthakur G, Martinelli G, Raffoux E, Chevallier P, Chromik J, Lithio A, Smith CL, Yuen E, Oakley GJ 3rd, Benhadji KA, DeAngelo DJ. Phase 1 study to evaluate Crenigacestat (LY3039478) in combination with dexamethasone in patients with T-cell acute lymphoblastic leukemia and lymphoma. Cancer. 2021 Feb 1;127(3):372-380. doi: 10.1002/cncr.33188. Epub 2020 Oct 27.
PMID: 33107983DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
There were no participants enrolled to Part B and Phase 2 of the study.
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
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
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 5, 2015
First Posted
August 7, 2015
Study Start
October 1, 2015
Primary Completion
January 15, 2018
Study Completion
January 15, 2018
Last Updated
September 11, 2019
Results First Posted
February 6, 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.
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.