E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma |
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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 | 22.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the antitumor activity of single-agent MOR00208 in adult patients with relapsed or refractory NHL who have received at least one prior therapy containing rituximab as one of the treatments. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the duration of response
2. To establish safety and tolerability of MOR00208
3. To assess the potential immunogenicity of MOR00208
4. To evaluate the pharmacokinetics and pharmacodynamics of MOR00208 in patients with relapsed or refractory NHL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients are male or female ≥ 18 years of age.
2. Patients have a histologically-confirmed diagnosis according to the Revised European American lymphoma/World Health Organization (REAL/WHO) classification, of the following B-cell lymphomas :
a. FL
b. Other indolent NHL (eg, MZL/MALT)
c. DLBCL
d. MCL NOTE: For transformed lymphomas, the subtype at screening (not at initial diagnosis) is relevant for the assignment to the respective subtype.
3. Patients’ NHL must have progressed after at least one prior rituximab-containing regimen.
4. Patients have at least one site of measurable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan defined as at least one lesion that measures at least 1.5 × 1.5 cm, Exception: For patients with MCL only, patients with nonmeasurable disease but evaluable sites (bone marrow, spleen, peripheral blood, gastrointestinal tract) can be enrolled.
5. Patients who have previously received an autologous stem cell transplantation must be at least 4 weeks post-transplant before study drug administration and must have exhibited a full haematological recovery.
6. Patients must have discontinued previous monoclonal antibody therapy (except rituximab) or radioimmunotherapy administration for at least 60 days before study drug administration.
7. Patients should be off rituximab for at least 14 days before the screening visit and be confirmed to have either no response or have disease progression after rituximab treatment.
8. Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline(Cheson response criteria).
9. Patients have a life expectancy of > 3 months.
10. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of < 3.
11. Patients must meet the following laboratory criteria at screening:
a. Absolute neutrophil count (ANC) ≥ 1.0 x 10E9/L
b. Platelet count ≥ 75 × 10E9/L without previous transfusion within 10 days of first study drug administration
c. Haemoglobin ≥ 8.0 g/dL (may have been transfused)
d. Serum creatinine < 2.0 x upper limit of normal (ULN)
e. Total bilirubin ≤ 2.0 × ULN
f. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
12. If a female of childbearing potential, a negative pregnancy test must be confirmed before enrolment and use of double-barrier contraception, oral contraceptive plus barrier contraceptive must be used during the study and for 3 months after the last dose, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
13. If a male, an effective barrier method of contraception must be used during the study and for 3 months after the last dose if the patient is sexually active with a female of childbearing potential.
14. The patients are able to comply with all study-related procedures, medication use, and evaluations.
15. The patients are able to understand and give written informed consent and comply with the study protocol. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with cytotoxic chemotherapy, immunotherapy, radiotherapy or other lymphoma-specific therapy within 14 days before the screening visit or if patient has not recovered from side effects of previous lymphoma-specific therapy.
2. Treatment with a systemic investigational agent within 28 days before the screening visit.
3. Previous treatment with an anti-CD19 antibody or fragments
4. Previous allogenic stem cell transplantation.
5. Known or suspected hypersensitivity to the excipients contained in the study drug formulation.
6. Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] classes III-IV), cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.
7. Patients with positive hepatitis serology (see also Section 9.5.2). Hepatitis B (HBV): Patients with positive serology for HBV, defined as positivity for hepatitis B surface antigen (HBsAg) or total anti-hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if HBV DNA is not detectable.
Hepatitis C (HCV): Patients with positive HCV serology (defined as positive for anti-HCV antibody [anti-HCV]) unless HCV-ribonucleic acid (RNA) is confirmed negative.
8. History of human immunodeficiency virus (HIV) infection.
9. Any active systemic infection (viral, fungal, or bacterial) requiring active parenteral antibiotic therapy within 4 weeks of study drug administration.
10. Current treatment with immunosuppressive agents other than prescribed corticosteroids (not more than 10-mg prednisone equivalent).
11. Major surgery or radiation therapy within 4 weeks before first study drug administration.
12. Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment in the investigator’s opinion.
13. History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.
14. Active treatment/chemotherapy for another primary malignancy within the past 5 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ).
15. Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control.
16. History of noncompliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) (complete remission [CR] + partial remission [PR]), assessed as per the 2007 International Working Group (IWG) response criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. After 40 patients
2. After 80 patients |
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E.5.2 | Secondary end point(s) |
1. Stable disease (SD), duration of response (DoR), time to progression (TTP), and progression-free survival (PFS)
2. Incidence and severity of AEs
3. Number and proportion of patients who potentially develop anti-MOR00208 antibodies and semiquantitative (anti-MOR00208 antibody titer determination of confirmed positive samples) anti-MOR00208 antibody assessments
4. Pharmacokinetics (apparent maximum serum concentration [Cmax], time to maximum serum concentration [tmax], apparent trough serum concentration before dosing [Cpd], area under the serum concentration versus time curve from time 0 to the time t of the last quantifiable concentration [AUC0-t], area under the serum concentration versus time curve from time 0 to infinity (extrapolated) [AUC0-∞], apparent terminal rate constant [λZ], apparent terminal half-life [t½], total body clearance [CL], volume of distribution during the terminal phase [Vz]), parameters determined using non-compartmental data analysis)
5. Absolute and percentage change from baseline in measurements of B,T- and natural killer (NK) cell populations
6. Evaluation of AEs and ORR stratified by baseline CD19 expression on malignant lymphoma cells
7. Evaluation of AEs and ORR stratified by (FcγR)IIIa and FcγRIIa polymorphism |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Germany |
Hungary |
Italy |
Poland |
Spain |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |