E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory chronic lymphocytic leukemia (CLL) |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or refractory chronic lymphocytic leukemia (CLL) |
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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 | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy (bendamustine) in patients with relapsed or refractory CLL (or SLL) who have progressed after one prior treatment with retuximab, has superior efficacy compared to rituximab in the same population. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability, antitumor activity, overall survival, pharmakokinectics and immunogenicitiy of MEDI-551 when used in combination with Bendamustine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Previous confirmation of B-cell CLL (including SLL) with a characteristic immunophenotype by flow cytometry.
• Progressive disease after receiving at least one prior line of treatment (a minimum of one course of chemotherapy with rituximab) and not a candidate for HSC or BM transplant
• Deemed a candidate for bendamustine/rituximab therapy by their treating physician
• Presence of symptomatic disease
• Adequate hematological function
• Adequate organ 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
• Exposure to Bendamustine within 180 days before drug administration
• Any active secondary malignancy
• Prior autologous or allogeneic stem cell transplantation SCT
• Clinically significant abnormality on ECG
• History of other invasive malignancy within 5 years except for localized/in situ, carcinomas such as cervical carcinoma in situ or basal/squamous skin cancer.
• Evidence of active infection
• Documented current central nervous system involvement by leukemia or lymphoma
• Having Richter’s transformation or high-grade disease
• Current pregnancy or lactation
• History of yellow fever vaccination within three months prior to study enrollment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the Overall Response Rate (ORR), including Complete Response (CR) and Partial Response (PR), in adult subjects with progressive CLL (or SLL) treated with up to 6 cycles of MEDI-551 in combination with bendamustine versus rituximab in combination with bendamustine. |
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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 (CR) rate, Minimal Residual Disease (MRD) negative CR rate, Time to Response (TTR), Time to Progression (TTP), Progression Free Survival (PFS); 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, Clearance (CL)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Antitumor activity: Study Day 720
Acceptable dose: Study Day 56
Safety and Tolerability: Study Day 720
IM: Up to Study Day 720
PK: Study Day 2, Study Day 8, Study Day 15, Study Day 22, Study Day 29, Study Day 57, Study Day 85, Study Day 113, Study Day 141, Study Day 169, Study Day 199, Study Day 229
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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 | 47 |
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 |
Canada |
France |
Germany |
Israel |
Italy |
Poland |
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) for the last subject in the study. This date will be after a combined total of 82 deaths occur in the rituximab arm and the selected MEDI-551 arm, or 24 months from the date the last subject is randomized into the study, or the date the sponsor stops the study, 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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |