E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory classical Hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
A cancer of the lymph glands that improved and then returned or did not improve in patients given with the usual treatments for this cancer |
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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 | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare progression free survival (PFS) as assessed by blinded independent central review, according to the American Society of Clinical Oncology International Working Group (IWG) response criteria [Cheson, 2007] between the treatment arms (pembrolizumab or brentuximab vedotin), including clinical and imaging data following autologous stem-cell transplantation (auto-SCT) or
allogeneic stem-cell transplantation (allo-SCT).
To compare overall survival (OS) between treatment arms.
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E.2.2 | Secondary objectives of the trial |
To compare PFS (PFS - secondary), as assessed by blinded independent central review, according to the IWG response criteria between treatment arms, excluding clinical and imaging data following auto-SCT or allo-SCT.
To compare the complete remission rate (CRR) as assessed by blinded independent central review according to the IWG response criteria [Cheson, 2007] between treatment arms.
To compare the overall response rate (ORR) as assessed by blinded independent central review according to the IWG response criteria [Cheson, 2007] between treatment arms.
To evaluate PFS, CRR, and ORR as assessed by the investigator according to the IWG response criteria [Cheson, 2007] by treatment arm.
To evaluate the safety and tolerability of pembrolizumab.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
– ≥18 years of age
– Relapsed or refractory classical Hodgkin lymphoma
– Measurable disease on spiral computed tomography (CT) or combined
CT/positron emission tomography (PET) scan
– Evaluable core or excisional lymph node biopsy
– Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
– Adequate organ function (laboratory studies)
– Negative pregnancy/lactation
– Adequate contraception (males and females)
Refer to the protocol for more detail on each inclusion criterion.
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E.4 | Principal exclusion criteria |
1. Has severe (≥ Grade 3) hypersensitivity to the active substance or to any of the excipients in BV or pembrolizumab. 2. Is currently participating in or has participated in a study of an investigational agent and is currently receiving study therapy or has participated in a study of an investigational agent and has received
study therapy or used an investigational device within 4 weeks of the first dose of treatment. 3. Has a diagnosis of immunosuppression or is receiving systemic steroid therapy (exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
4. Has had a prior monoclonal antibody within 4 weeks prior to first dose
of therapy in the study or who has not recovered (i.e., ≤Grade 1 or at
baseline) from AEs due to agents administered more than 4 weeks
earlier.
5. Has had prior chemotherapy, targeted small molecule therapy, or
radiation therapy including investigational agents within 4 weeks prior
to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline)
from AEs due to a previously administered agent.
6. Has undergone prior allo-SCT within the last 5 years.
7. Has a known additional malignancy that is progressing or has required
active treatment in the last 3 years.
8. Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain
metastases may participate provided they are radiologically stable (ie,
without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study
screening), clinically stable, and without requirement of steroid
treatment for at least 14 days prior to the first dose of trial treatment.
9. Has active autoimmune disease that has required systemic treatment
in the past 2 years (i.e., with the use of disease modifying agents,
corticosteroids, or immunosuppressive drugs).
10. Has a history of (non-infectious) pneumonitis that required steroids,
or current pneumonitis.
11. Has an active infection requiring intravenous systemic therapy.
12. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the trial.
13. Is pregnant or breastfeeding, or expecting to conceive or father
children within the projected duration of the trial, starting with the
screening visit through 120 days after the last dose of pembrolizumab or
180 days after the last dose of BV
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, CTLA-4 antibody (including ipilimumab), or OX-40, or any
other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways.
15. Has a known history of human immunodeficiency virus (HIV)
infection. No HIV testing is required unless mandated by local health
authority.
16. Has active hepatitis B (HBV) (e.g., HBsAg reactive) or hepatitis C
(HCV) (e.g., HCV RNA [qualitative] is detected).
17. Has received a live vaccine within 30 days prior to first dose.
18. Has a known history of active tuberculosis (TB; Bacillus
tuberculosis).
19. Is eligible for allogeneic or autologous stem cell transplantation per
investigator assessment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression-free Survival (PFS)
2. Overall survival (OS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 40 months
2. Up to approximately 40 months |
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E.5.2 | Secondary end point(s) |
1. Progression-free Survival (PFS - secondary)
2. Objective Response Rate (ORR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
U1. p to approximately 40 months |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Brazil |
Canada |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Russian Federation |
Singapore |
Turkey |
Ukraine |
United States |
Czechia |
Finland |
France |
Germany |
Italy |
Poland |
Sweden |
United Kingdom |
Spain |
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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
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If it is the last visit of the last subject, please enter "LVLS". If it is not LVLS provide the definition: LVLS |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |