Study to evaluate Effects of Daratumumab Monotherapy on Bone Parameters in Patients with Relapsed and /or Refractory Multiple Myeloma who Have Received at least 2 Prior Lines of Therapy including Lenalidomide and a Proteasome Inhibitor

Phase 1

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

• Registration Number: EUCTR2017-003951-44-GR
• Lead Sponsor: Hellenic Society of Hematology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-11-28
• Last Update Posted: 6 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 57

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 and / or refractory multiple myeloma as defined by the criteria below:
a)Measurable disease as defined by any of the following:
oSerum 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
oLight chain multiple myeloma for patients without measurable disease in the serum or urine by SPEP/UPEP: 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 including lenalidomide and a PI for MM (induction followed by any planned high dose therapy or consolidation or maintenance would be considered as one regimen).
5.Documented evidence of progressive disease (PD) as defined by the modified IMWG criteria on or after the last regimen.
6.Karnofsky Performance Status score of = 70.
7.All of the following laboratory test results during screening:
•Absolute neutrophil count (ANC) of = 1.0 x 109/L.
•Platelet count of = 75 x 109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells and =50 x 109/L in patients in whom = 50% of bone marrow nucleated cells are plasma cells.
•Hemoglobin level > 7.5 g/dL
•Alanine aminotransferase < 2.5 times the upper limit of normal (ULN).
8.Adequate renal function: estimated Glomerular Filtration Rate (eGFR) = 30 mL/min by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
9.Willingness and ability to participate in study procedures.
10.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.
b.Women must not be breastfeeding.
c.WOCBP must agree to follow instructions for effective 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.Male patients must 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 3 months post-treatment completion. The additional contraception of female partners of childbearing potential should also be considered.

Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. Subjects must agree to the use of two methods of contraception, with one method being highly effective (tubal ligation, intrauterine device [IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner’s vasectomy) and the other method being additionally effective (male latex or synthetic condom, diaphragm, or cervical cap).
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 17
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Patient has received any of the following therapies:
•Radiotherapy or systemic therapy within 2 weeks of baseline.
•Prior Allogeneic hematopoietic stem cell transplantation; or Autologous stem cell transplantation within 12 weeks of baseline.
•Prior Treatment with any CD38-antibody (i.e. daratumumab, isatuximab).
2.Clinically significant cardiac disease, including:
a)Myocardial infarction within 6 months, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
b)Cardiac arrhythmia (CTCAE Grade 3 or higher) or clinically significant ECG abnormalities.
c)ECG showing a baseline QT interval as corrected >470 msec.
3.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.
4.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)Patient is 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).
5.Patient is known to be seropositive for human immunodeficiency virus (HIV)

6.Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to enrolment.
7.Hypersensitivity to the active substance or to any of the excipients.
8.Any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with subject’s ability to give informed consent, the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
9.Pregnant or breastfeeding women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified