E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Multiple Myeloma |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with a type of blood cancer (multiple myeloma) that is either relapsed (comes back) or refractory (did not get better) after prior treatment. |
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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 | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028229 |
E.1.2 | Term | Multiple myelomas |
E.1.2 | System Organ Class | 100000004851 |
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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 |
Progression Free Survival |
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E.2.2 | Secondary objectives of the trial |
- Overall Survival - Very Good Partial Response or better response rate - Progression Free Survival in subjects with high BLC2 expression - Duration of response - Patient Reported Outcomes - Time to Progression - Overall Response Rate - Minimal Residual Disease Status - Safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 2. Subject has documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy. ● Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. ● Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of PD) while on primary or salvage therapy, or progresses within 60 days of last therapy. 3. Subject must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. ● A line of therapy consists of ≥ 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens. 4. Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: ● Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND ● Best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a PR, AND ● Subject did not discontinue any proteasome inhibitor due to intolerance or ≥ Grade 3 related toxicity. 5. Subject has measurable disease at Screening, defined as at least one of the following: ● Serum M-protein ≥ 0.5 g/dL, OR ● Urine M-protein ≥ 200 mg in 24-hours, OR ● Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
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E.4 | Principal exclusion criteria |
1. Subject is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen. 2. Subject has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug. 3. Subject has any of the following conditions: ● Non-secretory multiple myeloma ● Active plasma cell leukemia i.e., either 20% of peripheral white blood cells comprised of plasma cells or > 2.0 × 10^9/liter (L) circulating plasma cells by standard differential ● Waldenström's macroglobulinemia ● Amyloidosis ● POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) ● Known Human Immunodeficiency Viral (HIV) infection ● Active hepatitis B or C infection based on screening blood testing ● Significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of randomization, or congestive heart failure New York Heart Association (NYHA) Class ≥ 3 ● Major surgery within 4 weeks prior to randomization ● Acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to randomization ● Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to randomization ● Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization ● Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study 4. Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: ● Adequately treated in situ carcinoma of the cervix uteri or the breast ● Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin ● Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment ● Previous malignancy with no evidence of disease, confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study 5. If subject had prior stem cell transplant (SCT), subject has evidence of ongoing graft-versus-host disease (GvHD).
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When 136 Progression Free Survival events occur |
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E.5.2 | Secondary end point(s) |
Overall Survival Very Good Partial Response or better response rate Progression Free Survival in subjects with high BLC2 expression Duration of response Patient Reported Outcomes Time to Progression Overall Response Rate Minimal Residual Disease Status |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall Survival: when approximately 116 OS events are observed. Other secondary endpoints will be evaluated in the final analyses, following positive analysis for Progression Free Survival. |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Australia |
Brazil |
Canada |
Japan |
Korea, Republic of |
Russian Federation |
Ukraine |
United States |
Denmark |
France |
Germany |
Hungary |
Ireland |
Italy |
Spain |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |