E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated Multiple Myeloma |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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 |
The primary objective of Phase 2 is to select a dose of LY2127399 to assess with bortezomib and dexamethasone in Phase 3. The primary objective of Phase 3 is to compare PFS after treatment with the dose of LY2127399 selected in Phase 2, bortezomib, and dexamethasone, to that of placebo, bortezomib, and dexamethasone in patients with relapsed/refractory MM. |
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E.2.2 | Secondary objectives of the trial |
In addition to the primary objective of PFS, there will be 3 key secondary outcomes compared between treatments after the Phase 3 portion of the study, listed in order of precedence:
- Overall survival (OS)
- Time to first skeletal-related event (SRE)
- The incidence of clinically significant pain response
Additional secondary objectives for assessment at the end of the study (Section 4) are as follows:
- To compare the following efficacy variables between the treatment arms:
- Time to next treatment
- Time to progression
- Response rate and duration of response (if the study progresses to Phase 3)
- Progression-free survival (PFS) (if study does not progress to Phase 3)
- To describe the population PK of LY2127399 in patients with MM
- To describe the immunogenicity of LY2127399 in patients with MM
Exploratory Objectives
The exploratory objectives of the study are as follows:
- Biomarker objectives
- Health outcomes objectives
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Have symptomatic and/or progressive multiple myeloma that was previously treated with at least 1 and no more than 3 prior lines of therapy
-Have measurable disease
-Are ≥18 years of age
-Have given written informed consent prior to any study-specific procedures
-Have adequate organ function
-Treatment with prior autologous transplant is permitted
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E.4 | Principal exclusion criteria |
-Are enrolled in or discontinued from a clinical trial of any drug or device within 21 days prior to the first dose of assigned study treatment
• Have had less than a minimal response or have had progressive disease within 60 days of most recent therapy with a proteasome inhibitor.
• Plan to proceed to autologous transplant for consolidation after treatment on Study JDCG.
• Have an active infection or ongoing treatment for systemic infection (“ongoing treatment” does not include prophylactic anti-infectives), chest x-ray suggestive of tuberculosis, or history/risk of chronic/latent infection that may reactivate in the presence of study therapy.
• Have positive test results for human immunodeficiency virus (HIV), evidence of hepatitis B (positive for hepatitis B surface antigen, or positive for hepatitis B core antibody and negative for hepatitis B surface antibody) or positive test results of hepatits C virus (HCV; positive for anti-hepatitis C antibody). A positive test for HCV is defined as a) positive for hepatitis C antibody (HepCAb), and b) confirmed positive via the hepatitis C recombinant immunoblot assay.
• Have had significant allergy to human/humanized monoclonal antibodies that, in the opinion of the investigator, poses an unacceptable risk to the patient.
• Have known hypersensitivity or contraindication to any of the study therapies or excipients.
• Prior allogeneic hematopoietic stem cell transplant.
• Prior therapy with experimental agents targeting BAFF, including LY2127399.
• Have corrected QT (QTc) interval >500 msec on baseline 12-lead electrocardiogram (ECG).
• Have Waldenstrom’s macroglobulinemia.
• History of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the subject has been disease-free for at least 3 years.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of Phase 2 is to select a dose of LY2127399
The primary endpoint of Phase 3 is to compare PFS between the treatment arms
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 2 Primary Endpoint: 2 cycles after the last patient is enrolled to Phase 2
Phase 3 Primary Endpoint: at least 450 PFS events
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E.5.2 | Secondary end point(s) |
Phase 3 secondary Endpoint: overall survival |
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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 | 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 | 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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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
| 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 | 37 |
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 |
Brazil |
Canada |
Korea, Republic of |
Mexico |
Taiwan |
Turkey |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |