E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory diffuse large B-cell lymphoma(DLBCL) |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or refractory diffuse large B-cell lymphoma(DLBCL) |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell 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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine if MEDI-551, when used in combination with salvage chemotherapy, Ifosafamide-carboplatin-etoposide (ICE) or Dexamethasone-cytarabine (DHAP) in patients with relapsed or refractory DLBCL who are eligible for Autologous Sem Cell Tansplant (ASCT), has superior efficacy compared to rituximab in the same population.
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E.2.2 | Secondary objectives of the trial |
Evaluate anti-tumor activities and overall survival (OS),to determine an acceptable dose for MEDI-551 when used in combination with ICE or DHAP, to describe the safety and tolerability, to determine the immunogenicity (IM), and to describe the pharmacokinetic (PK) profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL
• Willing to provide some or all of archived DLBCL tumor sample if a sufficient sample quantity is available. If no archived sampleis available or no marrow involvement is present, an optional additional biopsy may be requested.
• Relapsed from or refractory to at least one treatment chemioterphy regimen containing rituximab
• Eligible for ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of ≥ 12 weeks
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from screening, and must agree to continue using such precautions after the final dose of investigational product for at least 180 days
• Adequate hematological function |
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E.4 | Principal exclusion criteria |
• Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment
• Previous MAb or other treatment specifically directed against CD19
• Prior autologous or allogeneic SCT
• New York Heart Association ≥ Class II congestive heart failure;
• History of other invasive malignancy within 5 years except for localized/in situ, carcinomas.
• Evidence of active infection, unless clinically stable per the investigator's evaluation
• Any inflammatory or immune-related disease that is not well-controlled on stable doses of medication for at least 10 days.
• Active hepatitis B as defined by seropositivity for hepatitis B surface antigen (HBsAG). Subjects with positive hepatitis B core antibody titers and normal liver transaminases are allowed provided that antiviral prophylaxixs is administered per institutional guidelines. Subjects with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis
• Documented current central nervous system involvement by leukemia or lymphoma |
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall response rate (ORR), including Partial Response (PR) and Complete Response (CR), of subjects treated with MEDI-551 when used in combination with ICE or DHAP versus rituximab in combination with ICE or DHAP in subjects with relapsed or refractory DLBCL. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Antitumor activity: Includes complete response rate, Minimal residual disease negative complete response rate, time to response (TTR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS)
Acceptable Dose: Benefit/Risk Analysis of Safety and Efficacy to be determined
Safety and Tolerability: The safety endpoints include Adverse Events (AEs), Serious Adverse Events (SAEs) occurring during the protocol-specified reporting period and changes in clinical laboratory evaluations, Electrocardiogram (ECGs), vital signs, and weight from baseline.
Immunogenicity (IM): Number and percentage of subjects who develop detectable anti-drug antibodies
Pharmacokinetics (PK): Area Under Curve, CMAX, T1-half
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Antitumor activity: Study Day 1080
Acceptable dose: Study Day 42
Safety and Tolerability: Study Day 1080
IM: Up to Study Day 1080
PK: Study Day 1; Study Day 8; Study Day 12; Study Day 19; Study Day 26; Study Day 54; Study Day 110; Study Day 138; Study Day 166 |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Poland |
Russian Federation |
Spain |
United States |
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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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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) in the study. This date will be after a total of 90 deaths occur in the selected MEDI-551 dose arm and the rituximab arm or 36 months after the date of randomization for the last subject, or the date the sponsor stops the trial, whichever occurs first. |
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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 | |
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 | 5 |
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 | 0 |