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A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02518113
Recruitment Status : Completed
First Posted : August 7, 2015
Results First Posted : February 6, 2019
Last Update Posted : September 11, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE August 5, 2015
First Posted Date  ICMJE August 7, 2015
Results First Submitted Date  ICMJE January 14, 2019
Results First Posted Date  ICMJE February 6, 2019
Last Update Posted Date September 11, 2019
Actual Study Start Date  ICMJE October 1, 2015
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up To 28 Days) ]
    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).
  • Recommended Dose of LY3039478 in Combination With Dexamethasone [ Time Frame: Cycle 1 (28 Days) ]
    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.
  • Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR) [ Time Frame: Baseline to Objective Disease Progression (Up To 2 Months) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 5, 2015)
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (28 Days) ]
  • Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR) [ Time Frame: Baseline to Objective Disease Progression (Approximately 2 Months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1 [ Time Frame: Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours ]
    Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination with Dexamethasone in Day 1
  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8 [ Time Frame: Cycle 1 Day 8: 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
  • Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
    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 participants achieving a CR or a CRi divided by the total number of participants 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.
  • Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
  • Phase 2: Number of Participants Who Achieve PR [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
  • Phase 2: Duration of Remission (DoR) [ Time Frame: Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year) ]
  • Phase 2:Relapse Free Survival (RFS) [ Time Frame: Date of CR to Relapse or Death from any Cause (Approximately 1 Year) ]
  • Phase 2: Event Free Survival (EFS) [ Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year) ]
  • Phase 2: Overall Survival (OS) [ Time Frame: Baseline to the Date of Death from Any Cause (Approximately 1.5 Years) ]
  • Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score [ Time Frame: Baseline, End of Study (Approximately 1.5 Years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2015)
  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3039478 in Combination with Dexamethasone [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (Approximately 4 Weeks) ]
  • Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations [ Time Frame: Baseline to Objective Disease Progression (Approximately 2 Months) ]
  • Number of Participants who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR [ Time Frame: Baseline to Objective Disease Progression (Approximately 2 Months) ]
  • Number of Participants who Achieve PR [ Time Frame: Baseline to Objective Disease Progression (Approximately 2 Months) ]
  • Duration of Remission (DoR) [ Time Frame: Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year) ]
  • Relapse Free Survival (RFS) [ Time Frame: Date of CR to Relapse or Death from any Cause (Approximately 1 Year) ]
  • Event Free Survival (EFS) [ Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year) ]
  • Overall Survival (OS) [ Time Frame: Baseline to the Date of Death from Any Cause (Approximately 1.5 Years) ]
  • Change from Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score [ Time Frame: Baseline, End of Study (Approximately 1.5 Years) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
Official Title  ICMJE A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • T-cell Acute Lymphoblastic Leukemia
  • T-cell Lymphoblastic Lymphoma
Intervention  ICMJE
  • Drug: LY3039478
    Administered orally
  • Drug: Dexamethasone
    Administered orally
  • Drug: Placebo
    Administered orally
Study Arms  ICMJE
  • Experimental: LY3039478 + Dexamethasone (Adult)

    Part 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.

    Interventions:
    • Drug: LY3039478
    • Drug: Dexamethasone
  • Experimental: LY3039478 + Dexamethasone (Pediatric)

    Part 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.

    Interventions:
    • Drug: LY3039478
    • Drug: Dexamethasone
  • Experimental: Phase 2: LY3039478 + Dexamethasone

    LY3039478 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:
    • Drug: LY3039478
    • Drug: Dexamethasone
  • Placebo Comparator: Phase 2: Placebo + Dexamethasone

    Placebo 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:
    • Drug: Dexamethasone
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 9, 2018)
36
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2015)
92
Actual Study Completion Date  ICMJE January 15, 2018
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Israel,   Italy,   United States
Removed Location Countries Australia,   Sweden,   Taiwan
 
Administrative Information
NCT Number  ICMJE NCT02518113
Other Study ID Numbers  ICMJE 14548
I6F-MC-JJCB ( Other Identifier: Eli Lilly and Company )
2014-005024-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (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.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP