Clinical Trials List
Protocol NumberI6F-MC-JJCB
NCT Number(ClinicalTrials.gov Identfier)NCT02518113
2016-11-01 - 2020-12-31
Phase II
Terminated2
ICD-10C91.02
Acute lymphoblastic leukemia, in relapse
ICD-10C83.50
Lymphoblastic (diffuse) lymphoma, unspecified site
A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination with Dexamethasone in T-ALL/T-LBL Patients
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Trial Applicant
ELI LILLY AND COMPANY(TAIWAN), INC.
-
Sponsor
Eli Lilly and Company
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Yu Lien Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
Co-Principal Investigator
- Su-Peng Yeh 未分科
Audit
None
Co-Principal Investigator
- 林建廷 Division of General Internal Medicine
- Chien-Chin Lin Division of Others -
- MING YAO Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- 李啟誠 Division of Hematology & Oncology
- 劉家豪 Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- Jih-Luh Tang Division of General Internal Medicine
- Tai-Chung Huang Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
T-cell Acute lymphoblastic leukemia(T-ALL)/r T-cell lymphoblastic lymphoma (T-LBL)
Objectives
The primary objective is as follows:
Phase 1: to determine the recommended dose of LY3039478 in combination with dexamethasone in adult
patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic
lymphoma (T-LBL) (Part A) and pediatric patients (Part B)
Phase 2: to determine if the overall remission rate (ORR) (CR plus CR with incomplete blood count
recovery [CRi]) in adult patients with relapsed/refractory T-ALL/T-LBL treated with LY3039478 in
combination with dexamethasone exceeds that of those patients treated with placebo in combination with
dexamethasone
Test Drug
LY3039478
Active Ingredient
LY3039478
Dosage Form
capsule
Dosage
25 or 50
Endpoints
Efficacy:
ORR
CR rate
proportion of patients achieving a CRi
proportion of patients achieving a PR
DoR
OS
RFS
EFS
Safety: Safety will be evaluated based on recorded adverse events (AEs), physical examinations, vital sign
measurements, electrocardiograms, and clinical laboratory assessments. Adverse events will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Adverse events and clinical laboratory values will be
graded using NCI CTCAE v4.0.
Health Outcomes: Patient health-related quality of life including physical, social/family, emotional and functional
well-being will be assessed using the self-administered FACT-Leu questionnaire at the beginning of each visit only
in the Phase 2 portion of the study.
Pharmacokinetics: Blood and CSF samples will be used to determine the concentrations of LY3039478. CSF
concentrations of LY3039478, and plasma concentrations of LY3039478 and dexamethasone will be quantified
using validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays. The remaining
plasma samples collected for PK evaluation may be used for exploratory studies to assess the metabolism of
LY3039478, which may involve sample pooling.
Pharmacodynamics/Tailoring Biomarkers: Blood, CSF, EDTA plasma, tissue, and bone marrow samples will be
collected. Samples will be tested for markers of Notch and related pathway activation including, but not limited to,
protein expression and activation by IHC and ELISA, and gene expression by quantitative polymerase chain
reaction (PCR) analysis to evaluate their association with the observed clinical outcomes to LY3039478.
ORR
CR rate
proportion of patients achieving a CRi
proportion of patients achieving a PR
DoR
OS
RFS
EFS
Safety: Safety will be evaluated based on recorded adverse events (AEs), physical examinations, vital sign
measurements, electrocardiograms, and clinical laboratory assessments. Adverse events will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Adverse events and clinical laboratory values will be
graded using NCI CTCAE v4.0.
Health Outcomes: Patient health-related quality of life including physical, social/family, emotional and functional
well-being will be assessed using the self-administered FACT-Leu questionnaire at the beginning of each visit only
in the Phase 2 portion of the study.
Pharmacokinetics: Blood and CSF samples will be used to determine the concentrations of LY3039478. CSF
concentrations of LY3039478, and plasma concentrations of LY3039478 and dexamethasone will be quantified
using validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays. The remaining
plasma samples collected for PK evaluation may be used for exploratory studies to assess the metabolism of
LY3039478, which may involve sample pooling.
Pharmacodynamics/Tailoring Biomarkers: Blood, CSF, EDTA plasma, tissue, and bone marrow samples will be
collected. Samples will be tested for markers of Notch and related pathway activation including, but not limited to,
protein expression and activation by IHC and ELISA, and gene expression by quantitative polymerase chain
reaction (PCR) analysis to evaluate their association with the observed clinical outcomes to LY3039478.
Inclution Criteria
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria
during screening prior to first dose of study drug.
[1] Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic
lymphoma (T-LBL).
T-ALL is defined by ≥25% of blasts in the bone marrow and expression of at
least 2 of the following cell surface antigens:
CD1a, CD2, CD3 (surface or cytoplasmic) CD4, CD5, CD7, and/or
CD8.
If the only T-cell markers present are CD4 and CD7, the leukemia cells must
also lack the myeloid markers CD33 and/or CD13.
[2] T-ALL or T-LBL patients with relapsed/refractory disease. Patients with
initial refractory disease should have received at least 2 multi-agent
chemotherapy induction regimens. Patients in first or second relapse must
have been refractory to at least 1 multi-agent chemotherapy reinduction
regimen.
[3] Have had at least 60 days between prior hematopoietic SCT and first dose of
study drug.
[4] Have a performance status of 0 to 2 on the Eastern Cooperative Oncology
Group (ECOG) scale (see Attachment 5) for adults.
[5] Lansky score >50% for patients <16 years old.
[6] Have adequate organ function:
hepatic: bilirubin 1.5 × the upper limit of normal (ULN) and ALT and
AST 3 × ULN. For patients with liver involvement, ALT and AST 5 ×
ULN
renal: calculated creatinine clearance ≥45 mL/min or a serum creatinine based on
age/gender (Attachment 6)
[7] 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.
[8a] 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.
[8b] 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.
[9] Have an estimated life expectancy of at least 2 months and in the judgment of
the investigator, will be able to complete at least 2 cycles of treatment.
[10] Have given written informed consent/assent prior to any study-specific
procedures.
All patients and/or their parents or legally authorized representatives must
sign a written ICF. Assent, when appropriate, will be obtained according
to institutional guidelines.
[11] Are able to swallow capsules and tablets.
Patients are eligible to be included in the study only if they meet all of the following criteria
during screening prior to first dose of study drug.
[1] Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic
lymphoma (T-LBL).
T-ALL is defined by ≥25% of blasts in the bone marrow and expression of at
least 2 of the following cell surface antigens:
CD1a, CD2, CD3 (surface or cytoplasmic) CD4, CD5, CD7, and/or
CD8.
If the only T-cell markers present are CD4 and CD7, the leukemia cells must
also lack the myeloid markers CD33 and/or CD13.
[2] T-ALL or T-LBL patients with relapsed/refractory disease. Patients with
initial refractory disease should have received at least 2 multi-agent
chemotherapy induction regimens. Patients in first or second relapse must
have been refractory to at least 1 multi-agent chemotherapy reinduction
regimen.
[3] Have had at least 60 days between prior hematopoietic SCT and first dose of
study drug.
[4] Have a performance status of 0 to 2 on the Eastern Cooperative Oncology
Group (ECOG) scale (see Attachment 5) for adults.
[5] Lansky score >50% for patients <16 years old.
[6] Have adequate organ function:
hepatic: bilirubin 1.5 × the upper limit of normal (ULN) and ALT and
AST 3 × ULN. For patients with liver involvement, ALT and AST 5 ×
ULN
renal: calculated creatinine clearance ≥45 mL/min or a serum creatinine based on
age/gender (Attachment 6)
[7] 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.
[8a] 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.
[8b] 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.
[9] Have an estimated life expectancy of at least 2 months and in the judgment of
the investigator, will be able to complete at least 2 cycles of treatment.
[10] Have given written informed consent/assent prior to any study-specific
procedures.
All patients and/or their parents or legally authorized representatives must
sign a written ICF. Assent, when appropriate, will be obtained according
to institutional guidelines.
[11] Are able to swallow capsules and tablets.
Exclusion Criteria
Exclusion Criteria
Potential study patients may not be included in the study if any of the following apply during
screening.
[12] Are currently enrolled in a clinical trial involving an investigational product or
nonapproved use of a drug or device (other than the study drug/device used in
this study), or concurrently enrolled in any other type of medical research
judged not to be scientifically or medically compatible with this study.
[13] Have discontinued prior anticancer therapy less than 2 weeks prior to starting
therapy or 5 half-lives (whichever is longer) with the following exceptions:
glucocorticoids administered as antileukemic treatment should be
discontinued at least 5 days prior to starting therapy
mercaptopurine may be dosed up to 5 days prior to first dose of
LY3039478
Vinca alkaloids may be dosed up to 7 days prior to first dose of
LY3039478
intrathecal chemotherapy may be dosed up to 7 days prior to first dose
of LY3039478
At the discretion of the investigator, hormone-sensitive prostate cancer
patients who are in remission and stable on gonadotropin-releasing
hormone (GnRH) agonist therapy and breast cancer patients who are
stable on antiestrogen therapy (for example, an aromatase inhibitor) may
have that treatment continued while they are enrolled in this study.
[14] Have previously completed or withdrawn from this study or any other study
investigating LY3039478 or other Notch inhibitors. (This exclusion criterion
does not apply to patients who are re-screened prior to
enrollment/randomization.)
[15] Have a serious concomitant systemic disorder that, in the opinion of the
investigator, would compromise the patient’s ability to adhere to the protocol.
[16] Have evidence of uncontrolled, active infection <7 days prior to
administration of study medication.
[17] Have current or recent (within 3 months of study drug administration) GI
disease with chronic or intermittent diarrhea, or disorders that increase the risk
of diarrhea, such as inflammatory bowel disease. Nonchronic conditions
(eg, infectious diarrhea) that are completely resolved for at least 1 week prior
to starting study treatment are not exclusionary.
[18] Have conditions requiring chronic systemic (not inhaled) glucocorticoid use,
such as autoimmune disease or severe asthma. Low doses of corticosteroids
are permitted.
[19] Have active (symptomatic or requiring current medical treatment) graft versus
host disease.
[20] Have active leukemic involvement of the CNS as shown by spinal fluid
cytology or imaging. A lumbar puncture is not required unless CNS
involvement is clinically suspected. Patients with signs or symptoms of
leukemic meningitis or a history of leukemic meningitis must have a blast-free
cerebrospinal fluid within 14 days of the first day of study treatment.
[21] Have a second primary malignancy or prior malignancy that, in the judgment
of the investigator and following consultation with Lilly, may affect the
interpretation of results. Patients with carcinoma in situ of any origin and
patients with prior malignancies who are in remission and whose likelihood of
recurrence is very low, as judged by the Lilly clinical research physician
(CRP), are eligible for this study. The Lilly CRP will approve enrollment of
patients with prior malignancies in remission before these patients are
enrolled.
Potential study patients may not be included in the study if any of the following apply during
screening.
[12] Are currently enrolled in a clinical trial involving an investigational product or
nonapproved use of a drug or device (other than the study drug/device used in
this study), or concurrently enrolled in any other type of medical research
judged not to be scientifically or medically compatible with this study.
[13] Have discontinued prior anticancer therapy less than 2 weeks prior to starting
therapy or 5 half-lives (whichever is longer) with the following exceptions:
glucocorticoids administered as antileukemic treatment should be
discontinued at least 5 days prior to starting therapy
mercaptopurine may be dosed up to 5 days prior to first dose of
LY3039478
Vinca alkaloids may be dosed up to 7 days prior to first dose of
LY3039478
intrathecal chemotherapy may be dosed up to 7 days prior to first dose
of LY3039478
At the discretion of the investigator, hormone-sensitive prostate cancer
patients who are in remission and stable on gonadotropin-releasing
hormone (GnRH) agonist therapy and breast cancer patients who are
stable on antiestrogen therapy (for example, an aromatase inhibitor) may
have that treatment continued while they are enrolled in this study.
[14] Have previously completed or withdrawn from this study or any other study
investigating LY3039478 or other Notch inhibitors. (This exclusion criterion
does not apply to patients who are re-screened prior to
enrollment/randomization.)
[15] Have a serious concomitant systemic disorder that, in the opinion of the
investigator, would compromise the patient’s ability to adhere to the protocol.
[16] Have evidence of uncontrolled, active infection <7 days prior to
administration of study medication.
[17] Have current or recent (within 3 months of study drug administration) GI
disease with chronic or intermittent diarrhea, or disorders that increase the risk
of diarrhea, such as inflammatory bowel disease. Nonchronic conditions
(eg, infectious diarrhea) that are completely resolved for at least 1 week prior
to starting study treatment are not exclusionary.
[18] Have conditions requiring chronic systemic (not inhaled) glucocorticoid use,
such as autoimmune disease or severe asthma. Low doses of corticosteroids
are permitted.
[19] Have active (symptomatic or requiring current medical treatment) graft versus
host disease.
[20] Have active leukemic involvement of the CNS as shown by spinal fluid
cytology or imaging. A lumbar puncture is not required unless CNS
involvement is clinically suspected. Patients with signs or symptoms of
leukemic meningitis or a history of leukemic meningitis must have a blast-free
cerebrospinal fluid within 14 days of the first day of study treatment.
[21] Have a second primary malignancy or prior malignancy that, in the judgment
of the investigator and following consultation with Lilly, may affect the
interpretation of results. Patients with carcinoma in situ of any origin and
patients with prior malignancies who are in remission and whose likelihood of
recurrence is very low, as judged by the Lilly clinical research physician
(CRP), are eligible for this study. The Lilly CRP will approve enrollment of
patients with prior malignancies in remission before these patients are
enrolled.
The Estimated Number of Participants
-
Taiwan
8 participants
-
Global
80 participants
