Daratumumab in combination with ATRA in patients with relapsed/ refractory multiple myeloma

Phase 1

• Conditions: relapsed/refractory multiple myeloma; MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003862-10-NL
• Lead Sponsor: VU University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-19
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Age 18 years and older
2. Subject must have documented multiple myeloma as defined by the criteria below:
•Monoclonal plasma cells in the bone marrow =10% at some point in their disease history or presence of a biopsy proven plasmacytoma.
•Measurable disease as defined by any of the following:
o Serum monoclonal paraprotein (M-protein) level =5 g/L (0.5 g/dL); or urine M-protein level =200 mg/24 hours; or serum immunoglobulin free light chain =100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio (See Appendix A)
3. Relapsed from or refractory to 2 or more different prior therapies, including IMiDs (eg, thalidomide, lenalidomide) and proteasome inhibitors, chemotherapy-based regimens, or ASCT and without further established treatment options.
--Relapse is defined as progression of disease after an initial response (MR or better) to previous treatment, more than 60 days after cessation of treatment
--Refractory disease is defined as < 25% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment
4. WHO performance 0, 1, or 2
5. Life expectancy at least 3 months
6. Written informed consent

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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion Criteria

1. Subject has received daratumumab or other anti-CD38 therapies, within 6 months before start of treatment.
2. Non-secretory myeloma
3. Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom’s macroglobulinemia
4. Subject has known meningeal involvement of multiple myeloma
5. Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before start of treatment. This included subjects who have received a cumulative dose of corticosteroid greater than or equal to the equivalence of 140 mg prednisone or a single dose of corticosteroid greater than or equal to the equivalence of 40 mg/day dexamethasone within the 2-week period before start of treatment.
6. Subject has previously received an allogeneic stem cell transplantation within 1 year before the date of registration and has not used immunesuppressive drugs within one months before the date of registration.
7. Inadequate marrow reserve as defined by a platelet count <50 x 109/L or an absolute neutrophil count <1.0 x 109/L
8. a) Subject has known chronic obstructive pulmonary disease (COPD) with an Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
b) Subject has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
9. Subject has clinically significant cardiac disease, including:
•Myocardial infarction within 6 months before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable
angina, congestive heart failure, New York Heart Association Class III-IV)
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Version 4 Grade 2 or higher) or clinically significant ECG abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >470 msec.
10. Significant hepatic dysfunction (total bilirubin = 3 times normal value or transaminases = 3 times normal value), unless related to myeloma
11. Creatinine clearance <30 ml/min.
12. Known hypersensitivity to components of the investigational product or severe allergic or anaphylactic reactions to humanized products.
13. Subject has any concurrent severe and/or uncontrolled medical condition (e.g.uncontrolled diabetes, infection, hypertension, etc.) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
14. Subject is known to be seropositive for human immunodefiency virus (HIV) or have active hepatitis B or hepatitis C.
15. History of active malignancy during the past 5 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 5 years.
16. Subject is known or suspected of not being able to comply with the study protocol
(eg, because of alcoholism, drug dependency, or psychological disorder)

Study & Design

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