E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non Hodgkin's or Hodgkin's lymphoma |
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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 |
Dose escalation phase Primary objective: 1.To determine the maximum tolerated dose (MTD) or the recommended Phase II dose of HCD122 when administered as a single agent intravenously (IV) once weekly for 4 weeks to adult patients with advanced non-Hodgkin’s or Hodgkin’s lymphoma who have progressed after at least two prior therapies
Dose expansion phase Primary objective: 1.To assess clinical response at the MTD or the recommended phase II dose in adult patients with advanced non-Hodgkin’s or Hodgkin’s lymphoma who have progressed after at least two prior therapies
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E.2.2 | Secondary objectives of the trial |
Dose escalation phase: Main Secondary objective: 1.To characterize safety and tolerability of single agent HCD122, including acute and chronic toxicities 2.To characterize the pharmacokinetic (PK) profile after single and repeated doses of single agent HCD122 on a once weekly dosing schedule for 4 weeks 3.To assess the immunogenicity of HCD122 4.To characterize the CD40 occupancy profile of HCD122 on peripheral CD19(+) B cells after single and repeated doses
Dose expansion phase: Main Secondary objectives: 1.To characterize safety and tolerability of single agent HCD122, including acute and chronic toxicities 2.To characterize the pharmacokinetic (PK) profile after single and repeated doses of single agent HCD122 on a once weekly dosing schedule for 4 weeks for the first 40 patients in dose expansion phase 3.To assess the immunogenicity of HCD122 4.To characterize the CD40 occupancy profile of HCD122 on peripheral CD19(+) B cells after single and repeated doses
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients must have confirmed diagnosis, according to the Revised European American Lymphoma/World Health Organization [REAL/WHO] classification, of the following B-cell lymphomas: 1.Follicular lymphoma (FL) 2.Marginal zone lymphoma (MZL)/mucosa-associated lymphoid tissue (MALT) 3.Diffuse large B-cell lymphoma (DLBCL) 4.Mantle cell lymphoma (MCL), OR 5.Hodgkin lymphoma (HL) •Patients must have progressed after at least 2 prior therapies (autologous stem cell transplantation is considered as 1 therapy): 1.Patient must receive at least one prior therapy with a rituximab containing regimen if it is indicated as the standard of care 2.If patient received autologous stem cell transplantation, patient must have received at least 1 prior systemic therapy 3.If patient did not receive autologous stem cell transplantation, patient must have received at least 2 prior systemic therapies •Patients who received autologous stem cell transplantation: 1.Must be at least 12 weeks post-transplant prior to study drug, AND 2.Must have recovered fully from the side effects of such treatment prior to beginning study treatment. •Patients who have NOT received autologous stem cell transplantation: 1.Must be ineligible for the autologous stem cell transplantation, OR 2.If eligible, patients chose not to receive stem cell transplant •Patients must have discontinued any previous anticancer and investigational therapy including radiation therapy for at least 21 days prior to study drug, and must have recovered fully from the side effects of such treatment prior to beginning study drug. •Patients must have discontinued previous monoclonal antibody (except rituximab) or radioimmunotherapy administration for at least 60 days prior to study drug, and are confirmed either have no response to that therapy or have disease progression after the treatment. Patients must have recovered fully from the side effects of that treatment prior to beginning study treatment. For patients who received rituximab containing regimen, rituximab should be discontinued for at least 28 days prior to study drug, are confirmed to either have no response or have disease progression after rituximab treatment, and must have recovered fully from the side effects of such treatment prior to beginning study drug. •Patients must not have undergone major surgery within 30 days prior to study drug, and must have recovered fully from the side effects of any major or minor surgical procedures prior to study treatment. •Patients must be 18 years
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E.4 | Principal exclusion criteria |
•Patients who have been treated with any anti-CD40 antibody •Patients who have received prior allogeneic stem cell transplant •Patients who have had a prior anaphylactic or other severe infusion reaction such that the patient is unable to tolerate human immunoglobulin or monoclonal antibody administration •Patients who are taking systemic corticosteroids, except for a dose up to 100 mg of hydrocortisone or equivalent as premedication administered prior to certain medications or blood products •Patients who have current drug or alcohol abuse •Patients who have history or clinical evidence of central nervous system, meningeal, or epidural disease including brain metastasis •Impaired cardiac function or clinically significant cardiac disease, including any one of the following: 1.New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant arrhythmia, congestive heart failure, or cardiomyopathy 2.Angina pectoris ≤ 3 months prior to starting study drug 3.Acute MI ≤ 3 months prior to starting study drug 4.Other clinically significant heart disease (e.g., uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) •Patients who have history of pancreatic disease (e.g., acute or chronic pancreatitis, etc.) or any surgery of the pancreas •Patients who have gallbladder stone, cystic fibrosis, or any other risk factors that may increase the risk of pancreatitis •Patients who have history of active infection (viral, bacterial, or fungal) requiring systemic therapy within 4 weeks prior to enrollment. Prophylactic antibiotics and anti-viral therapies are permitted
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose escalation phase: Incidence rate of DLT
Dose expansion phase: Response rate according to the 2007 Cheson criteria |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 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 | No |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Information not present in EudraCT |
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 |
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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
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Study completion is defined as participation in the study through week 16 (day 106) and completion of the week 16 (day 106) study visit. Discontinuation prior to this time point constitutes early discontinuation from the study ( for details see protocol Section 6.6.12). At week 16 (day 106), patients showing a best disease response of stable disease or achieve a response (PR or CR) during the study will have the option of retreatment with HCD122. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |