Skip to main content
OpenTrials
Completed

NCT Number: NCT02518113

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

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

T-cell Acute Lymphoblastic Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma T-Cell Lymphoblastic Lymphoma

Age range

2 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

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, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

LY3039478

Drug

Administered orally

Dexamethasone

Drug

Administered orally

Placebo

Drug

Administered orally

Primary outcomes

  1. 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).

  2. 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.

  3. 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.

Secondary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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)

  5. Phase 2: Number of Participants Who Achieve PR

    Time frame: Baseline to Objective Disease Progression (Up To 12 Months)

  6. 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)

  7. Phase 2:Relapse Free Survival (RFS)

    Time frame: Date of CR to Relapse or Death from any Cause (Approximately 1 Year)

  8. Phase 2: Event Free Survival (EFS)

    Time frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year)

  9. Phase 2: Overall Survival (OS)

    Time frame: Baseline to the Date of Death from Any Cause (Approximately 1.5 Years)

  10. 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)

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Aug 7, 2015
Registry last updated
Sep 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.