T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL)
Conditions
Interventions
Product Name: Notch II Inhibitor
Product Code: LY3039478
Pharmaceutical Form: Capsule, hard
Other descriptive name: LY3039478
Concentrat
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must have T-ALL or T-LBL. T-ALL is defined =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. 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. They must have had at least 60 days between prior hematopoietic stem cell transplant and first dose of study drug, have adequate performance status and organ function, be =16 years old for the adult cohort (Phase 1, Part A) and 2 to =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Patients may be excluded if they are currently enrolled in another ongoing clinical trial with investigational products, have recently discontinued (within less than 2 weeks) prior anticancer therapy, have a serious concomitant illness, have an uncontrolled or active infection <7 days prior to administration of study drug, have current or recurrent (within 3 months) gastrointestinal disease, have conditions requiring chronic systemic glucocorticoid use, have active graft versus host disease, have active leukemic involvement of the central nervous system, or have a second primary or prior malignancy that would affect the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase 1: Number of participants with dose limiting toxicities (DLTs) Phase 2: Overall Remission Rate ; Timepoint(s) of evaluation of this end point: Phase 1: Baseline to disease progression or patient discontinuation Phase 2: Baseline to study completion ; Main Objective: Phase1: 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) Phase2: 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 ;Secondary Objective: Phase1:Characterize the safety and toxicity profile of LY3039478 in combination with dexa as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0; Assess the PK parameters of LY in combination with dexa therapy; Document efficacy based on Cheson criteria for leukemia and modified response criteria for malignant lymphoma; Evaluate gene mutation status with efficacy. Phase2:Compare the ORR plus partial remission PR and PR alone for both arms; Assess the remission rate for patients receiving LY in combination with dexa after failure of placebo in combination with dexa; Assess DoR=CR and Cri and PR; Assess relapse-free survival, event-free survival, and overall survival; Compare the safety and toxicity profile of LY in combination with dexa to dexa and placebo as assessed by NCI CTCAE v 4.0; Assess the PK parameters of LY and dexa in combination therapy; Assess patient quality of life using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu); | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase1: 1)Number of participants with one or more drug related Adverse Events (AEs) or any Serious AEs 2)Pharmacokinetics: maximum concentration (Cmax) of LY3039478 in combination with Dexamethasone 3)Pharmacokinetics: area under the concentration curve (AUC) of LY3039478 in combination with Dexamethasone 4)Overall Remission Rate Phase2: 1)Overall Remission Rate plus Partial Remission Rate 2)Partial Remission Rate 3)Duration of Remission 4)Relapse Free Survival 5)Event free survival 6)Overall Survival 7)Number of participants with one or more drug related Adverse Events (AEs) or any Serious AEs 8)Pharmacokinetics: maximum concentration (Cmax) of LY3039478 in combination with Dexamethasone 9)Pharmacokinetics: area under the concentration curve (AUC) of LY3039478 in combination with Dexamethasone 10)FACT-Leu ; Timepoint(s) of evaluation of this end point: Phase 1: 1) Baseline to study completion 2) and 3) pre-dose to 6 hours post dose 4) baseline to study completion Phase 2: 1), 2) Baseline to study completion 3), 4) Date of remission to date of relapse or death 5) Date of study enrolment to date of relapse after remission, death or treatment failure 6)Date of study enrolment to date of death 7)Baseline to study completion 8), 9) pre-dose up to 8 hours post dose 10) baseline to end of cycle 1 | — |
Countries
Australia, France, Germany, Israel, Italy, Netherlands, Sweden, Taiwan, Turkey, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed