A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
- Conditions
- T-cell Acute Lymphoblastic LeukemiaT-cell Lymphoblastic Lymphoma
- Interventions
- Registration Number
- NCT02518113
- Lead Sponsor
- Eli Lilly and Company
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
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T-ALL or T-LBL participants with relapsed/refractory disease.
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Have had at least 60 days between prior hematopoietic stem cell transplantation (SCT) and first dose of study drug.
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Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale for adults.
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Lansky score >50% for participants <16 years old.
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Have adequate organ function.
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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
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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.
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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.
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Are able to swallow capsules and tablets.
- Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY3039478 + Dexamethasone (Adult) LY3039478 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. Phase 2: LY3039478 + Dexamethasone LY3039478 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. Phase 2: LY3039478 + Dexamethasone 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. Phase 2: Placebo + Dexamethasone Placebo 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. LY3039478 + Dexamethasone (Pediatric) LY3039478 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. LY3039478 + Dexamethasone (Pediatric) Dexamethasone 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. LY3039478 + Dexamethasone (Adult) Dexamethasone 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. Phase 2: Placebo + Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) 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 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) 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 Outcome Measures
Name Time Method 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 Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC\[0- 48\]) of LY3039478 in Combination with Dexamethasone in Day 8
Phase 2: Overall Survival (OS) Baseline to the Date of Death from Any Cause (Approximately 1.5 Years) 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) Phase 2: Duration of Remission (DoR) Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year) Phase 2: Event Free Survival (EFS) Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year) 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\[0-∞\]) of LY3039478 in Combination with Dexamethasone in Day 1
Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations 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:Relapse Free Survival (RFS) Date of CR to Relapse or Death from any Cause (Approximately 1 Year) Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score Baseline, End of Study (Approximately 1.5 Years)
Trial Locations
- Locations (11)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Texas MD Anderson
🇺🇸Houston, Texas, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Johann Wolfgang Goethe-Universität Frankfurt
🇩🇪Frankfurt, 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.
🇮🇹Torino, Italy
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, 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.
🇮🇱Tel Aviv, Israel
Montefiore Medical Center
🇺🇸Bronx, New York, United States