Efficacy of Daratumumab in Patients with Relapsed/Refractory Myeloma with Renal Impairment

Phase 1

Conditions: Relapsed/Refractory Myeloma with Renal Impairment
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-003950-18-IT

Lead Sponsor: HELLENIC SOCIETY OF HEMATOLOGY

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 38

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 documented relapsed or refractory multiple myeloma as defined by the criteria
below:
a) Monoclonal plasma cells in the bone marrow = 10% or presence of a biopsy proven
plasmacytoma.
b) Measurable disease as defined by any of the following:
o Serum monoclonal paraprotein (M-protein) level = 1.0 g/dL (except for IgA subtype: =
0.5 g/dL) or urine M-protein level = 200 mg/24 hours; or
o Light chain multiple myeloma: Serum immunoglobulin free light chain = 10 mg/dL and
abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
4. Prior treatment with at least two lines of treatment that included both bortezomib- and
lenalidomide-based regimens.
5. Documented evidence of progressive disease (PD) as defined by the IMWG 2014 on or after the
last regimen if the patient responded to previous regimens.
6. Renal impairment defined as eGFR < 30 ml/min/1.73 m2 (calculated with the CKD-EPI formula) or in need for dialysis. Patients who undergo intraperitoneal dialysis may also be included.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of = 2.
8. Willingness and ability to participate in study procedures.
9. Reproductive Status
a) Women of childbearing potential (WOCBP) must have two negative serum or urine
pregnancy tests, one 10-14 days prior to start of the study drug and one within 24 hours prior
to the start of study drug. 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 treatment with study drugs, for the duration of treatment with study drugs, and for
3 months after cessation of study treatment.
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 contraception for 4
weeks before the start of treatment with study drugs, for the duration of treatment with study
drugs, and for a total of 90 days post-treatment completion. The additional contraception of female partners of childbearing potential should also be considered.
e) Male patients must not donate sperm for up to 90 days post treatment completion.
f) Female patients must not donate eggs for up to 90 days post treatment completion.
g) Azoospermic males and WOCBP who are not heterosexually active are exempt from
contraceptive requirements. However, WOCBP will still undergo pregnancy testing
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

1. Previous therapy with daratumumab or other anti-CD38 therapy.
2. Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1.
3. Cumulative dose of corticosteroids greater than or equal to the equivalent of 140mg prednisone
for =4 days or a dose of corticosteroids greater than or equal to the equivalent of 40 mg/day of
dexamethasone for =4 days within the 2-week period prior to Cycle 1, Day 1.
4. Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within
12 weeks before Cycle 1, Day 1.
5. Clinical signs of meningeal involvement of multiple myeloma.
6. Chronic obstructive pulmonary disease (COPD), persistent asthma, or a history of asthma within
5 years.
7. Clinically significant cardiac disease, including:
a) Myocardial infarction within 1 year, or unstable or uncontrolled condition (e.g., unstable
angina, congestive heart failure, New York Heart Association Class III-IV).
b) Cardiac arrhythmia (CTCAE Grade 2 or higher) or clinically significant ECG abnormalities.
c) ECG showing a baseline QT interval as corrected by Fridericia¿s formula (QTcF) >470 msec.
8. Any of the following:
a. Known active hepatitis A
b. Patient is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) 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 (anti-HBs 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. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
9. Known to be seropositive for human immunodeficiency virus (HIV).
10. Amyloidosis, or any prior or concurrent malignancy, except for the following:
a) Adequately treated basal cell or squamous cell skin cancer.
b) Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior
to study entry.
11. Any 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);
c) Platelet count <75 × 109/L in patients in whom <50% of bone marrow nucleated cells are
plasma cells and <50x109/L in patients in whom more than 50% of bone marrow nucleated
cells are plasma cells;
d) Alanine aminotransferase level =2.5 times the upper limit of normal (ULN);
12. Pregnant or nursing women.

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

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