E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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 |
The primary objective is to determine the efficacy of 2 treatment regimens of daratumumab, as measured by the overall response rate (ORR) (complete response [CR] + partial response [PR]),
in subjects with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of daratumumab.
To assess the pharmacokinetics of drug product.
To evaluate duration of and time to response to daratumumab.
To determine the clinical benefit (CR+PR+MR) rate following treatment with daratumumab.
To evaluate clinical outcomes including time to disease progression (TTP), PFS, and OS.
To assess the pharmacokinetics, pharmacodynamics, and generation of antibodies to daratumumab (immunogenicity).
To explore biomarkers predictive of response to daratumumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Principal Inclusion Criteria in Lay Language (for a complete list of
inclusion criteria refer to the protocol):
- Documented multiple myeloma according to protocol-defined criteria
- Evidence of disease progression based on International Myeloma Working Group criteria
- Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
- Laboratory values and electrocardiogram within protocol-defined parameters at screening |
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E.4 | Principal exclusion criteria |
Principal Exclusion Criteria in Lay Language (for a complete list of
exclusion criteria refer to the protocol):
- Received daratumumab or other anti-CD38 therapies previously
- Nonsecretory multiple myeloma
- Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
- Exhibiting clinical signs of meningeal involvement of multiple myeloma
- Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
- Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
- Has plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 6 months after the last participant is enrolled in the study |
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E.5.2 | Secondary end point(s) |
For a full list of secondary end point refer to protocol:-
1. Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
2. Duration of response
3. Overall survival
4. Clinical benefit rate
5. Time to response
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For a full list of timepoint(s) of evaluation of secondary endpoint refer to protocol:-
1. Up to 30 days after the last dose of study medication
2. From the date of initial documentation of a response (complete
or partial response) to the date of first documented evidence
of progressive disease as defined by International Myeloma
Working Group criteria
3. From the date of the first dose of daratumumab administered
to the date of the participant’s death
4. Up to 8 weeks after the last dose of daratumumab
administered
5. From the first dose of daratumumab administered and the first
efficacy evaluation that the participant has met all criteria for
complete or partial response
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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 | No |
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 | No |
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) | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
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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
|
The study is considered completed 18 months after the last subject receives the first dose of daratumumab. The final data from the study site will be sent to the sponsor (or designee) after completion of the final subject assessment at that study site, in the time frame specified in the Clinical Trial Agreement. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |