| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Peripheral T-cell Lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Peripheral T-cell lymphoma (PTCL) is a rare, aggressive type of non-Hodgkin lymphoma. PTCL generally affects people aged 60 years and older and is diagnosed slightly more often in men than in women. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| 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 | 10042971 |
| E.1.2 | Term | T-cell lymphoma |
| 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 |
Dose Optimization Phase
• To determine the optimal duvelisib dose for utilization in the Expansion Phase by evaluating the ORR supported by safety, additional efficacy, and pharmacokinetics (PK) parameters as well as any other available data in the population of patients receiving the optimal dose of duvelisib for at least one cycle in patients with relapsed or refractory PTCL
Expansion Phase
• To determine the efficacy of the optimal dose of duvelisib in patients with relapsed or refractory PTCL |
|
| E.2.2 | Secondary objectives of the trial |
Dose Optimization Phase
• To evaluate additional efficacy parameters for duvelisib in the population of patients receiving duvelisib for at least one cycle in patients with relapsed or refractory PTCL
• To characterize the tolerability and safety of duvelisib in patients with relapsed or refractory PTCL
• To evaluate the PK of duvelisib and if applicable, its metabolite(s)
Expansion Phase
• To evaluate additional efficacy parameters for duvelisib
• To characterize the tolerability and safety of duvelisib in patients with relapsed or refractory PTCL
• To evaluate the PK of duvelisib and if applicable, its metabolite(s) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥ 18 years of age
2. Pathologically-confirmed PTCL, as defined by the World Health Organization. Slides must be submitted for central pathology review. Results of central pathology review are not required prior to initiation of treatment.
3. Received at least 2 cycles of one standard regimen for newly diagnosed advanced PTCL, and one of the following:
(a) failed to achieve at least a partial response after 2 or more cycles of standard therapy; (b) failed to achieve a complete response after completion of standard therapy; and/or
(c) persistent or progressive disease after an initial response
4. For patients with CD30+ anaplastic large cell lymphoma (ALCL), failed or are ineligible or intolerant to brentuximab vedotin
5. Measurable disease as defined by Lugano (Cheson et al, 2014) for PTCL, i.e., at least 1 measurable disease lesion > 1.5 cm in at least one dimension by conventional techniques (18FDG-PET-CT, CT with contrast, MRI)
6. Must have the following laboratory parameters:
(a) Hemoglobin ≥ 8.0 g/dL with or without transfusion support
(b) Platelet count ≥ 25 × 109/L
(c) Serum creatinine ≤ 2.0 × the upper limit of normal (ULN)
(d) Total bilirubin ≤ 1.5 × ULN (in patients with Gilbert's Syndrome a bilirubin > 1.5 × ULN may be allowed)
(e) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN
(f) Expansion Phase Only: CD4 lymphocyte count ≥ 50/mm3 (0,05 x 109/L)
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
8. Recovery to ≤ Grade 1 or baseline for any toxicities due to prior treatments, with the exception of peripheral neuropathy (recovery to ≤ Grade 2) or alopecia
9. Washout of at least 14 days or 5 half-lives, whichever is longer, from PTCL-directed therapy. If previously treated with lenalidomide, must have completed treatment 4 weeks prior to C1D1
10. For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women > 55 years of age)
11. Male and female patients, of reproductive potential (i.e., not surgically sterile or female patients who are not postmenopausal) must be willing to use a highly effective method of contraception for the duration of study treatment, and for at least 3 months after the last dose of duvelisib
12. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)/central ethics committee (CEC)-approved informed consent form before any Screening procedures are performed |
|
| E.4 | Principal exclusion criteria |
1. Primary leukemic PTCL subtypes (i.e., T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma, and aggressive NK-cell leukemia) or transformed mycosis fungoides
2. Received prior allogeneic transplant
3. Received prior treatment with a PI3K inhibitor
4. Major surgery within 4 weeks prior to Screening
5. Known central nervous system involvement by PTCL
6. Infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or Human T-lymphotropic virus type 1 (HTLV-1). (Patients with a positive hepatitis B surface antigen [HBsAg] or hepatitis C antibody [HCV Ab] will be excluded. Patients with a positive hepatitis B core antibody [HBcAb] must have negative hepatitis B virus [HBV] deoxyribonucleic acid (DNA) to be eligible, must receive prophylaxis with entecavir [or equivalent] concomitant with duvelisib treatment, and must be periodically monitored for HBV reactivation by institutional guidelines. Investigators who strongly believe that that a positive HBcAb is false due to passive immunization from previous immunoglobulin infusion therapy should discuss the potential to defer HBV prophylaxis with the Medical Monitor.)
7. Active cytomegalovirus (CMV) infection (patients with detectable viral load)
8. History of tuberculosis treatment within 2 years prior to C1D1
9. History of chronic liver disease, veno-occlusive disease, or alcohol abuse
10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) once daily (QD)
11. Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening
NOTE: Patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met
12. Administration of a live vaccine within 6 weeks of C1D1
13. Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A)
14. Unable to receive prophylactic treatment for pneumocystis at Screening
15. Baseline left ventricular ejection fraction (LVEF) < 50% (or below institution’s normal limit)
16. Baseline QT interval corrected with Fridericia’s method (QTcF) > 480 ms
NOTE: criterion does not apply to patients with a right or left bundle branch block
17. Prior surgery or condition with gastrointestinal dysfunction that may significantly affect drug absorption (e.g., gastric bypass surgery, gastrectomy, clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting)
18. If female, pregnant or breastfeeding
19. Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix
NOTE: Patients with previous malignancies are eligible if disease-free for > 2 years.
20. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to Screening
21. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator’s judgment, increase the risk to the patient associated with his or her participation in the study.
22. Known hypersensitivity to duvelisib and/or its excipients. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Dose Optimization Phase
• Objective response rate (Complete response + Partial response), as assessed by the Investigator, as determined using the Lugano criteria (Cheson et al, 2014), supported by secondary efficacy, safety and PK in the population of patients receiving the optimal dose of duvelisib for at least one cycle of study therapy
Expansion Phase
• Objective response rate (Complete response + Partial response), as assessed by the Independent Review Committee, according to Lugano criteria (Cheson et al, 2014) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Throughout the whole study |
|
| E.5.2 | Secondary end point(s) |
Dose Optimization Phase
• Duration of response (DOR), for those patients with CR or PR, defined as the time from the first documentation of response to the first documentation of progressive disease (PD), or death due to any cause
• Treatment-emergent adverse events (TEAEs) and changes in laboratory values
• Progression-free survival (PFS), defined as the time from the first study drug dose to the first documentation of PD, or death from any cause
• Disease control rate (DCR), defined as CR + PR + stable disease ≥ 8 weeks,
• Overall survival (OS)
• PK parameters derived from blood concentrations of duvelisib and its metabolites
Expansion Phase
• TEAEs and changes in laboratory values
• DOR, for those patients with CR or PR, defined as the time from the first documentation of response to the first documentation of PD, or death due to any cause
• PFS, defined as the time from the first dose of study treatment to the first documentation of PD, or death from any cause
• DCR, defined as CR + PR + SD ≥ 8 weeks,
• OS
• PK parameters derived from blood concentrations of duvelisib and its metabolites |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the whole study |
|
| 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 | No |
| 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 | No |
| 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) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
| Japan |
| United Kingdom |
| United States |
| Germany |
| Italy |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | 22 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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