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).
Brief Title
A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
Categories
Completion Date
Completion Date Type
Actual
Conditions
T-cell Acute Lymphoblastic Leukemia
T-cell Lymphoblastic Lymphoma
Eligibility Criteria
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* Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.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).
* 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).
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
2 Years
NCT Id
NCT02518113
Org Class
Industry
Org Full Name
Eli Lilly and Company
Org Study Id
14548
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
Primary Outcomes
Outcome Description
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).
Outcome Measure
Number of Participants With Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Cycle 1 (Up To 28 Days)
Outcome Description
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.
Outcome Measure
Recommended Dose of LY3039478 in Combination With Dexamethasone
Outcome Time Frame
Cycle 1 (28 Days)
Outcome Description
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.
Outcome Measure
Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR)
Outcome Time Frame
Baseline to Objective Disease Progression (Up To 2 Months)
Secondary Ids
Secondary Id
I6F-MC-JJCB
Secondary Id
2014-005024-10
Secondary Outcomes
Outcome Description
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC\[0-∞\]) of LY3039478 in Combination with Dexamethasone in Day 1
Outcome Time Frame
Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours
Outcome Measure
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1
Outcome Description
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC\[0- 48\]) of LY3039478 in Combination with Dexamethasone in Day 8
Outcome Time Frame
Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours
Outcome Measure
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8
Outcome Description
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.
Outcome Time Frame
Baseline to Objective Disease Progression (Up To 12 Months)
Outcome Measure
Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations
Outcome Time Frame
Baseline to Objective Disease Progression (Up To 12 Months)
Outcome Measure
Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR
Outcome Time Frame
Baseline to Objective Disease Progression (Up To 12 Months)
Outcome Measure
Phase 2: Number of Participants Who Achieve PR
Outcome Time Frame
Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year)
Outcome Measure
Phase 2: Duration of Remission (DoR)
Outcome Time Frame
Date of CR to Relapse or Death from any Cause (Approximately 1 Year)
Outcome Measure
Phase 2:Relapse Free Survival (RFS)
Outcome Time Frame
Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year)
Outcome Measure
Phase 2: Event Free Survival (EFS)
Outcome Time Frame
Baseline to the Date of Death from Any Cause (Approximately 1.5 Years)
Outcome Measure
Phase 2: Overall Survival (OS)
Outcome Time Frame
Baseline, End of Study (Approximately 1.5 Years)
Outcome Measure
Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
LEUKEMIA, LYMPHOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
CRENIGACESTAT
DEXAMETHASONE
COUNTERFEIT DRUGS
PREGNADIENETRIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
STEROIDS, FLUORINATED
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS