E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory diffuse large B-cell lymphoma |
|
E.1.1.1 | Medical condition in easily understood language |
Relapsed or refractory diffuse large B-cell lymphoma (cancer of B cells, a type of white blood cell) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012821 |
E.1.2 | Term | Diffuse large B-cell lymphoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
The primary objective of Phase 1 is to evaluate the safety and tolerability of INCB039110 in combination with ibrutinib in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The primary objective of Phase 2 is to evaluate the efficacy of INCB039110 in combination with ibrutinib in subjects with relapsed or refractory non-GCB DLBCL as demonstrated by ORR. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of Phase 1 is to evaluate the efficacy of INCB039110 in combination with ibrutinib in terms of objective response rate (ORR).
The secondary objectives of Phase 2 are as follows:
• To evaluate efficacy in terms of duration of response (DOR), durable response rate, progression-free survival (PFS), and overall survival (OS).
• To evaluate the safety and tolerability of the treatment combination. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female, 18 years or older.
• Histologically documented diagnosis of DLBCL.
- For Phase 1, subjects may have any DLBCL subtype.
- For Phase 2, subjects must have ABC or unclassifiable subtypes of DLBCL confirmed by immunohistochemistry using the Hans algorithm.
• Relapsed or refractory DLBCL, defined as having received at least 1 but no more than 3 prior treatment regimens and ineligible for high-dose chemotherapy/autologous stem cell transplant.
• Fluorodeoxyglucose-avid disease (based on local evaluation) per the Lugano Classification. Fluorodeoxyglucose-avid disease is defined as disease with a 5-point scale score of 4 or 5. |
|
E.4 | Principal exclusion criteria |
• Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue lymphoma).
• Primary mediastinal (thymic) large B-cell lymphoma.
• Known central nervous system lymphoma (either primary or metastatic).
• Autologous stem cell transplant within the previous 3 months, allogeneic stem cell transplant within the previous 6 months, or active graft versus host disease following allogeneic transplant. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 : Safety and tolerability will be assessed by evaluating the frequency, duration, and severity of AEs (including serious adverse events [SAEs] and dose-limiting toxicities [DLTs]), and changes in clinical and laboratory assessments.
Phase 2 : Efficacy will be assessed by ORR, defined as the percentage of subjects achieving either a CR or PR. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1: Adverse events will be monitored from the time the subject signs the ICF through the safety follow-up. A DLT will be defined as the occurrence of any toxicities occurring up to and including Day 28.
Phase 2 : Week 8, Week 16, and every 16 weeks thereafter until disease progression.
|
|
E.5.2 | Secondary end point(s) |
Phase 1 : Efficacy will be assessed by ORR, defined as the percentage of subjects achieving either a complete response (CR) or partial response (PR).
Phase 2 :
• DOR, defined as the time from earliest date of disease response until earliest date of disease progression.
• Durable response rate, defined as the percentage of subjects achieving a CR or PR for > 16 weeks.
• PFS, defined as the time from enrollment until the earliest date of disease progression determined by objective radiographic disease assessments, or death due to any cause.
• OS, defined as the date of enrollment until death due to any cause.
• Safety and tolerability via assessment of the frequency, duration, and severity of AEs and SAEs, and changes in clinical and laboratory assessments. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse events will be monitored from the time the subject signs the ICF through the safety follow-up.
Efficacy endpoints: Week 8, Week 16, and every 16 weeks thereafter until disease progression. |
|
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 | No |
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 |
evaluate the safety and tolerability of INCB039110 in combination with ibrutinib |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Belgium |
France |
Italy |
Netherlands |
United Kingdom |
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
|
The end of Phase 1 will occur when all subjects have completed the DLT surveillance period; Phase 2 will end once the last subject is assessed for response. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 5 |