A clinical study to compare the effectiveness and pharmacokinetics (the way the body absorbs, distributes, and gets rid of a drug) of Daratumumab given through the subcutaneous route versus the intravenous route in patients with relapsed or refractory multiple myeloma (blood cancer in the bone marrow)
- Conditions
- Multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000206-38-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 480
1. Subjects with at least 18 years of age
2. Subjects who documented with multiple myeloma as defined by the
criteria below:
a)Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b)Measurable disease at Screening as defined by any of the following:
i) Serum M-protein level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or ii) Light chain multiple myeloma without measurable disease in the serum or the urine:Serum immunoglobulin FLC =10 mg/dL and abnormal serumimmunoglobulin kappa lambda FLC ratio.
3. Evidence of a response (partial response [PR] or better based on investigator’s determination of response by IMWG criteria) to at least 1 prior treatment regimen.
4. Relapsed or refractory disease as defined below:
a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed PD by IMWG criteria greater than (>) 60 days after cessation of treatment.
b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or > 60 days after cessation of treatment.
5. Received at least 3 prior lines of therapy including a PI (>= 2 cycles or 2 months of treatment) and an IMiD (>= 2 cycles or 2 months of treatment) in any order during the course of treatment (except for subjects who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). 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 OR Refractory to both a PI and an IMiD. For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMiD, their disease must be refractory to the most recent one.
6. Eastern cooperative oncology group (ECOG) performance Status score of 0, 1, or 2
7. Subjects who has pretreatment clinical laboratory values meeting the following criteria during the screening phase:
a) Hemoglobin >= 7.5 gram per decilitre (g/dL) (>= 5 millimoles per litre [mmol/L])
b) Absolute neutrophil count >= 1.0 × 10^9/Litre (L)
c) Platelet count >= 50 × 10^9/L
d) Aspartate aminotransferase (AST) <= 2.5 × upper limit of normal (ULN)
e) Alanine aminotransferase (ALT) <= 2.5 × ULN
f) Total bilirubin <= 2.0 × ULN; except in subjects with congenital bilirubinemia, such as Gilbert syndrome
g) Estimated creatinine clearance > 20 milliletre per minute (mL/min) per 1.73m^2
h) Albumin-corrected serum calcium <=14 mg/dL (<= 3.5 mmol/L) or free ionized calcium <= 6.5 mg/dL (<=1.6 mmol/L).
8. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously.
9. Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization.
10. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in
1. Subjects who received daratumumab or other anti-CD38 therapies previously.
2. Subjects who received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization.
3. Subjects who received autologous stem cell transplant within 12 weeks before the date of randomization, or the subject has previously received allogeneic stem cell transplant
4. Subjects who has plans to undergo a stem cell transplant prior to progression of disease on this study
5.History of malignancy if all treatment of that malignancy was completed at least 2 years
6. Subjects with clinical signs of meningeal involvement of multiple myeloma.
7. Subjects with either of the following:
a) Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) is <50% of predicted normal.
b) Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification
8. Subjects with any of the following:
a)Known to be HIV
b)Known to be 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
c)Known to be seropositive for hepatitisC;
9. Subjects with concurrent medical or psychiatric condition or disease 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.
10. Subjects with clinically significant cardiac disease, including:
a) Myocardial infarction within 6 months before date of randomization, 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).
b) Uncontrolled cardiac arrhythmia (Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
c) Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula >470 msec.
11. Subjects with known allergies, hypersensitivity, or intolerance to any of the study drugs, hyaluronidase, mAbs, human proteins, or their excipients, or known sensitivity to mammalian-derived products.
12. Subjects with plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) or amyloidosis.
13. Subjects with known or suspected of not being able to comply with the study protocol or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments.
14. Subjects who are pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug.
15. Subjects who has plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
16. Subjects who received an investigational drug or used an invasive investigational medical device within
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara-SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara- IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).;Secondary Objective: - To assess the pharmacokinetics and immunogenicity of Dara-SC and<br>Dara-IV<br>- To evaluate the safety of Dara-SC and Dara-IV<br>- To evaluate the clinical benefit of Dara-SC and Dara-IV<br>- To evaluate the immunogenicity of rHuPH20 following Dara-SC administration<br>- To evaluate patient-reported satisfaction with Dara-SC and Dara-IV;Primary end point(s): •ORR<br>•Maximum Ctrough;Timepoint(s) of evaluation of this end point: Cycle 3 Day 1 predose
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ¿Rate of infusion-related reactions (IRRs)<br>¿Progression-free survival (PFS)<br>¿Rate of very good partial response (VGPR) or better<br>¿Rate of complete response (CR) or better<br>¿Time to next therapy (TNT)<br>¿Overall survival (OS)<br>¿Patient-reported satisfaction with therapy<br>¿Duration of response<br>¿Time to response;Timepoint(s) of evaluation of this end point: There is no interim analysis planned for the primary or secondary endpoints. Both sets of endpoints will be analyzed 6 months after the last subject has been randomized