E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Multiple Myeloma (MM). |
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E.1.1.1 | Medical condition in easily understood language |
Blood cancer formed by malignant plasma cells that develops in the bone marrow and is non-responsive to therapy or relapses following 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 | 21.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective:
Part1 (Safety Run-in): To assess the safety of the combination of JNJ-63723283 and daratumumab.
Part 2 (Phase 2): To compare the overall response rate (ORR) in subjects treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone.
Part 3 (Phase 3): To compare progression-free survival (PFS) in subjects treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone.
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E.2.2 | Secondary objectives of the trial |
Phase 2 & Phase 3:
-To assess the safety of of the combination of JNJ 63723283 and daratumumab.
-To compare the complete response (CR)/better rate & very good partial response (VGPR)/better rate; duration of response and time to response; the minimal residual disease (MRD)-negative rate of JNJ-63723283 in combination with daratumumab versus daratumumab alone.
-To evaluate the pharmacokinetic & immunogenicity profile of JNJ-63723283 in combination with daratumumab & the profile of daratumumab alone or in combination with JNJ-63723283.
-To compare PFS & OS of JNJ-63723283 in combination with daratumumab versus daratumumab alone.
-To evaluate the ORR & OS.
-To assess the disease-related symptoms,functioning,quality of life (QOL) and health status by using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) & European Quality of Life 5 Dimensions Questionnaire (EQ-5D-5L).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
As of 25 May 2018, this study is closed to further enrollment.
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. At least 18 years of age.
2. Have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) in any order during the course of treatment for multiple myeloma or have disease that is refractory to both a PI and an IMiD. (For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one.Similarly, for those who have received more than 1 type of IMiD, their disease must be refractory to the most recent one).
3. Evidence of a response to at least 1 prior treatment regimen.
4. Documented measurable disease for multiple myeloma at screening as defined by the criteria below:
-IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
-IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
-Light chain multiple myeloma without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
5. Have relapsed or refractory disease at time of enrollment as defined below:
•Relapsed disease is defined as an initial response to previous treatment, followed by progressive disease (PD) by International Myeloma Working Group (IMWG) criteria >60 days after cessation of treatment.
•Refractory disease is defined as <25% reduction in M-protein or PD by IMWG criteria during previous treatment or ≤60 days after cessation of treatment.
6. Eastern Cooperative Oncology Group Performance Status (ECOG)performance status score of 0, 1, or 2.
7. Adequate organ function (bone marrow, liver, renal)
8. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
9. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
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E.4 | Principal exclusion criteria |
Any potential subject who meets any of the following criteria will be excluded from the study:
1. Received any of Anti-CD38 antibody, including daratumumab or Anti-PD-1 and anti-PD-L1 antibodies in the past.
2. Clinically significant cardiac or pulmonary disease.
3. Prior diagnosis of autoimmune disease with the exception of subjects:
- With autoimmune thyroid disease or type 1 diabetes that is well controlled on a stable medication regimen
- With vitiligo, alopecia, or resolved childhood asthma/atopy
- With psoriasis not requiring systemic therapy
- With transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent.
3. Unresolved Grade 2 or higher toxicity effects from previous treatment with immunotherapy not recovered to Grade ≤1 or baseline
4. Received any of the following prescribed medications or therapies within the specified period:
- Antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, prior to first administration of study drug. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment prior to first administration of study drug.
- An allogenic stem cell transplant (SCT) at any time; or autologous SCT within 12 weeks prior to first administration of study drug.
- Other investigational agent (including investigational vaccines), participation in another clinical study with therapeutic intent, or used an invasive investigational medical device within 28 days or 5 pharmacokinetic half-lives of the investigational agent (whichever is longer) prior to first administration of study drug.
- Systemic radiotherapy within 14 days prior to first administration of study drug.
5. Plans to undergo a stem cell transplant prior to progression of disease on this study.
6. History of malignancy (other than multiple myeloma) within 2 years prior to first administration of study drug
7. Known or suspected of not being able to comply with the study protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of adverse events (including dose-limiting toxicities (DLTs) (Part 1 [Safety Run-in] Group)
2. Overall response rate (ORR; as defined by IMWG response criteria (Part 2 [Phase 2] group)
3. Progression-free survival (PFS) (Part 3 [Phase 3] group) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Evaluation after 6 subjects have received 1 treatment cycle (28 days).
2. Evaluation after 80 subjects have received at least 4 treatment cycles.
3. Primary Analysis after 138 PFS events.
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E.5.2 | Secondary end point(s) |
Phase2 & Phase 3 Groups:
1. Incidence of adverse events, including immune-related AEs and infusion-related reactions
2. Complete response (CR) or better rate (as defined by the IMWG response criteria)
3. Very good partial response (VGPR) or better rate (as defined by the IMWG response criteria)
4. Duration of response
5. Time to response
6. Progression-free survival (PFS)
7. Incidence of anti-JNJ-63723283 antibodies
8. Incidence of anti-daratumumab antibodies
9. Overall survival (OS)
10. MRD-negative rate
11. Serum JNJ-63723283 Concentration (Cmin, Cmax)
12. Serum daratumumab pharmacokinetic Concentration (Cmin, Cmax)
Part 3 (Phase 3) Group:
13. Overall response rate (ORR)
14. Change from baseline in disease-related symptom scales, functioning scales, and Global Health Status (GHS) scale of the EORTC QLQ-C30, and the utility scale and visual analog scale (VAS) of the EQ-5D-5L
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 50 subjects have been enrolled and have been treated for at least 8 weeks or discontinued the study treatment
2 to 8. Part 2: At 12 months; Part 3: At 138 events
9. Part 2: At 12 months; Part 3: After 205 deaths have been observed
10. At the time of disease progression & at every 6 months in subjects with maintained CR & stringent complete response (sCR)
11. Cycle (C)1 Day (D)1, C1 D2, D1 of C 2,3,5, 7,12,16 & 24; every 12 cycles thereafter until end of treatment (EOT)
12. C1 D1, C1 D2, D1 of C 2,3,5, 7,12&24; every 12 cycles thereafter until EOT
13. Part 2: At 12 months; Part 3: At 138 events
14. D1 of every 3rd cycle (Cycles 3,6,9,12) until progressive disease (PD)
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Biomarker Analyses. |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Israel |
Russian Federation |
Turkey |
United States |
Belgium |
France |
Germany |
Greece |
Spain |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 22 |