A clinical study to evaluate the safety, effectiveness and pharmacokinetics of Daratumumab given through the subcutaneous route in combination with standard bone marrow cancer treatment regimens

Phase 1

Active, not recruiting

• Conditions: Multiple Myeloma; MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004203-41-ES
• Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-14
• Last Update Posted: 18 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

Each potential subject must satisfy all the following criteria to be enrolled in the study:
1. =18 years of age (or the legal age of consent if it is higher than 18 years of age in the jurisdiction in which the study is taking place)
2. Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
3. Measurable, secretory disease as defined by any of the following:
• Serum M-protein level =1.0 gram per decilitre (g/dL); or
• Urine M-protein level =200 mg/24 hours; or
• Light chain MM, for subjects without measurable disease in the serum or urine: serum Ig freel light chain (FLC) =10 milligrams per decilitre (mg/dL) and abnormal FLC ratio
4. Meets one of the sets of the following criteria:
a. For inclusion into the D-VRd cohort for newly diagnosed disease:
- Newly diagnosed MM by IMWG criteria and eligible/planned for high-dose therapy and autologous stem cell transplant (ASCT)
b. For inclusion into the D-VMP cohort:
- Newly diagnosed and previously untreated MM by IMWG criteria and not considered a candidate for high-dose chemotherapy with ASCT due to:
• Being age =65 years, or
• In subjects <65 years: presence of important comorbid condition(s) will make stem cell transplant intolerable for the subject. Sponsor review of these comorbid conditions and approval is required before the first dose of study treatment
c. For inclusion into the D-Rd cohort for relapsed or refractory disease:
- Relapsed disease is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment
- Refractory disease is defined as <25% reduction in M-protein or confirmed progressive disease (PD) by IMWG criteria during previous treatment or =60 days after cessation of treatment
- Subject must have received at least 1 prior line of therapy for MM
- A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy.
- Subjects must have progressed from or be refractory to their last line of treatment
- Subject must have achieved a response (partial response [PR] or better based on investigator’s determination of response by the IMWG criteria) to at least 1 prior regimen in past
5. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2
6. Pretreatment clinical laboratory values during the Screening Phase (all cohorts):
a) hemoglobin =7.5 g/dL (=4.65 mmol/L) (without prior red blood cell [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
b) absolute neutrophil count =1.0 × 10^9/L (prior growth factor support is permitted);
c) platelet count =50 × 10^9/L;
d) aspartate aminotransferase =2.5 × upper limit of normal (ULN);
e) alanine aminotransferase =2.5 × ULN;
f) total bilirubin =2.0 × ULN; except in subjects with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin =2.0 × ULN is required);
g) estimated creatinine clearance =40 mL/min (D-VMP cohort) or =30 mL/min (for D-VRd and D-Rd cohorts)
h) corrected serum calcium =14 mg/dL (=3.5 mmol/L) or free ionized calcium =6.5 mg/dL (=1.6 mmol/L)
7. D-VRd and D-Rd cohorts: A woman of childbearing potential must have 2 negative serum o

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study:
1. Prior or concurrent exposure to any of the following:
• Daratumumab or other anti-CD38 therapies
• Approved or investigational treatments for MM (including but not limited to conventional chemotherapies, immunomodulatory drugs [IMiDs], or proteasome inhibitors [PIs]) within 2 weeks of Cycle 1 Day 1
• Maximum of 40 mg dexamethasone (or equivalent) daily for a maximum of 4 days up to 21 days prior to the 1st dose
• Investigational drug (including investigational vaccines) or an invasive investigational medical device within 4 weeks or 5 half-lives (whichever is longer) before Cycle 1 Day 1, or is currently enrolled in another investigational study
• Refractory to lenalidomide, (ie, subjects who had progression of disease while receiving lenalidomide therapy or within 60 days of ending lenalidomide therapy) or who are intolerant to lenalidomide (ie, discontinued due to any drug-related adverse event) while on lenalidomide treatment are not eligible for the lenalidomide-containing cohorts
• ASCT within 12 weeks before the date of administration of study treatment, or allogeneic stem cell transplant (regardless of timing) for the D-Rd cohort
• Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within the 2-week period before the administration of study treatment
2. History of malignancy (other than multiple myeloma) if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease (exceptions are squamous and basal cell carcinomas of the skin and 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)
3. Exhibits clinical signs of meningeal involvement of MM
4. Either of the following:
• Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is <50% of predicted normal. Note that FEV1 testing also is required for subjects suspected of having chronic obstructive pulmonary disease (COPD) and subjects must be excluded if FEV1 is <50% of predicted normal
• Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification (Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study)
5. Any of the following:
• Seropositive for human immunodeficiency virus;
• Hepatitis B (hepatitis B surface antigen [HBsAg] positive, or antibodies to hepatitis B surface or core antigens [antiHBs or antiHBc] with hepatitis B virus [HBV]-DNA quantitation positive). Subjects who are positive for antiHBs or antiHBc must have a negative polymerase chain reaction (PCR) for HBV-DNA quantitation result at screening. Those who are PCR positive will be excluded
6. 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)
7. 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

Study & Design

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