Study to compare Pomalidomide and Dexamethasone With or Without Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor.
- Conditions
- Relapsed or Refractory Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001618-27-GR
- Lead Sponsor
- Stichting European Myeloma Network (EMN)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 302
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 free light chain (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 = 2;
8. Willingness and ability to participate in study procedures;
9. For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to =Grade 1;
10. All of the following laboratory test results during Screening:
a) Absolute neutrophil count =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% of bone marrow nucleated cells are plasma cells and platelet count =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 =2.5 times the upper limit of normal (ULN);
e) Aspartate aminotransferase (AST) level =2.5 x ULN;
f) Total bilirubin level =1.5 x ULN, (except for Gilbert Syndrome: direct bilirubin =1.5 × ULN);
g) Creatinine clearance =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 always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy. They must also agree to follow instructions for methods of
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) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. (Appendix 4);
8. Clinically significant cardiac disease, including:
a) Myocardial infarction within 6 months, before C1D1, or unstable or uncontrolled condition (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV);
b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) or clinically significant electrocardiogram (ECG abnormalities;
c) Electrocardiogram showing a baseline QT interval as corrected QTc >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 pulmonary disease) that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study;
14. Ongoing = Grade 2 peripheral neuropath
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method