| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic
lymphoma (T-LBL)
|
|
| E.1.1.1 | Medical condition in easily understood language |
| Leukemia and Lymphoma or blood cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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 |
|
| E.2.2 | Secondary objectives of the trial |
| 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); |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 <16 years old for the pediatric cohort (Phase 1, Part B), and have a life expectancy of 2 months. |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1: Number of participants with dose limiting toxicities (DLTs)
Phase 2: Overall Remission Rate |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1: Baseline to disease progression or patient discontinuation
Phase 2: Baseline to study completion |
|
| E.5.2 | 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 |
|
| E.5.2.1 | 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 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Phase 1 Dose-escalation - Phase II |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| France |
| Germany |
| Israel |
| Italy |
| Netherlands |
| Sweden |
| Taiwan |
| Turkey |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Occurs after study completion and after the last patient has discontinued study treatment and completed continued access period follow-up (if applicable). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 60 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 60 |
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