Kahler's disease plasma cell myeloma
Conditions
Interventions
Please refer to the section 7.2 of the protocol (TABLE 7.3: SCHEDULE OF EVENTS
and TABLE 7.3.1)
Sponsors
European Myeloma Network (EMN)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Males and females at least 18 years of age. 2. Voluntary written informed consent before performance of any study-related procedure. 3. Subject must have measurable disease of MM as defined by the criteria below: • IgG multiple myeloma: Serum M protein level >=1.0 g/dL or urine M-protein level >=200 mg/24 hours, or • IgA, IgD, IgE, IgM multiple myeloma: Serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hours; or • Light chain multiple myeloma, for subjects without measurable disease in the serum or urine: Serum immunoglobulin FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. 4. Subjects must have received prior anti-myeloma treatment. The prior treatment must have included both a PI- and lenalidomide-containing regimens. The subject must have had a response (ie, PR or better based on the investigator*s determination of response as defined by the modified IMWG criteria) to prior therapy. 5. Subjects must have documented evidence of PD based on the investigator*s determination of response as defined by the modified IMWG criteria on or after the last regimen. 6. Subjects who received only 1 line of prior treatment must have demonstrated PD on or within 60 days of completion of the lenalidomide containing regimen (ie, lenalidomide refractory). 7. Eastern Cooperative Oncology Group (ECOG) performance status score of =1.0 × 109/L; b) Hemoglobin level >=7.5 g/dL (>=4.65 mmol/L) (transfusions are not permitted to reach this level); c) Platelet count >=75 × 109/L in subjects in whom =50 x 109/L in subjects in whom >=50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted to reach this level); d) Alanine aminotransferase (ALT) level =30 mL/min (Appendix 6); h) Serum calcium corrected for albumin <=14.0 mg/dL (<=3.5 mmol/L), or free ionized calcium <=6.5 mg/dL (<=1.6 mmol/L). 11. Criterion (letter *g*) modified per Amendment 2: 11.1 Reproductive Status a) Women of childbearing potential (WOCBP) must have 2 negative serum or urine pregnancy tests, one 10-14 days prior to start of study treatment and one within 24 hours prior to the start of study treatment. Females are not of reproductive potential if they have been in natural menopause for at least 24 consecutive months, or have had a hysterectomy and/or bilateral oophorectomy. b) Women must not be breastfeeding. c) WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of study treatment, for the duration of study treatment, and for 3 months after cessation of daratumumab or 4 weeks after cessation of pomalidomide, whichever is longer. d) Males who are sexually active must al
Exclusion criteria
Exclusion criteria: 1. Previous therapy with any anti-CD38 monoclonal antibody. 2. Previous exposure to pomalidomide. 3. Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. 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 before Cycle 1, Day 1 (C1D1). 4. Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1. 5. History of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years). 6. Clinical signs of meningeal involvement of MM. 7. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) 470 msec. 9. Criterion modified per Amendment 2: 9.1 Known: a) Active hepatitis A b) To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. c) To be seropositive for hepatitis C (except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy).10. Criterion Revised per Amendment 2 10.1 Known to be seropositive for human immunodeficiency virus. 11. Gastrointestinal disease that may significantly alter the absorption of pomalidomide. 12. Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström*s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. 13. Any concurrent medical or psychiatric condition or disease (eg, active systemic infection, uncontrolled diabetes, acute diffuse infiltrative
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint - * Progression-free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints • Overall response rate • VGPR or better • Complete response (CR) or better • MRD negativity rate • Time to response • Duration of response (DoR) • Time to next therapy • Overall survival • Safety (adverse events) • Scale and domain scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) (global health status, physical functioning, emotional functioning, fatigue, pain) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20) (disease symptoms, side effects of treatment) • European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) health utility values • Immunomodulatory effects of daratumumab on T cells • Daratumumab pharmacokinetic concentrations (Dara IV and Dara SC) • Daratumumab and rHuPH20 immunogenicity in subjects who receive Dara SC | — |
Countries
Netherlands
Outcome results
None listed