A phase 2 study to compare Daratumumab in combination with Carfilzomib and Dexamethasone compared with Carfilzomib and Dexamethasone in participants with multiple myeloma previously treated with Daratumumab.
- Conditions
- MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Multiple MyelomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004185-34-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 230
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. At least 18 years of age.
2. Documented multiple myeloma as defined by the criteria below:
Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria.
Measurable disease at screening as defined by any of the following: Serum M-protein level >=1.0 g/dL in participants with immunoglobulin G (IgG) type, or serum M-protein level >=0.5 g/dL in participants with non- IgG type, or urine M-protein level >=200 mg/24 hours; or Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
3. Evidence of a response (partial response or better based on investigator’s determination of response by IMWG criteria) to daratumumab-containing IV therapy with response duration of at least 4 months.
4.1 Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined below:
Relapsed disease is defined as an initial response to previous treatment, followed by confirmed PD by IMWG criteria >60 days after cessation of treatment.
Refractory disease is defined as <25% reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or 60 days after cessation of treatment.
5. Received 1 or 2 prior line(s) of treatment of which one contained Dara-IV, and completed Dara-IV at least 3 months prior to randomization. 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.
6. ECOG Performance Status score of 0, 1, or 2.
7. Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
a) hemoglobin >=8 g/dL (>=5mmol/L) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
b) absolute neutrophil count (ANC) >=1.0 × 10^9/L (prior growth factor support is permitted but must be without support within the 7 days prior to the laboratory test);
c) platelet count >=75 ×10^9/L for participants in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count of >=50×10^9/L. Transfusions are not permitted within 7 days of testing to achieve this minimum platelet count.
d) aspartate aminotransferase (AST) <=2.5 × upper limit of normal (ULN);
e) alanine aminotransferase (ALT) <=2.5 × ULN;
f) total bilirubin <=1.5 × ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5× ULN is required);
g) estimated creatinine clearance (CrCl) >=20mL/min per 1.73m^2. CrCl to be calculated using estimated glomerular filtration rate Modification of Diet in Renal Disease (MDRD) formula.
h) albumin-corrected serum calcium <=14 mg/dL (<=3.5 mmol/L) or free ionized calcium <=6.5 mg/dL (<=1.6mmol/L)
For full inclusion criteria modified (n. 8.1 and 10.1), refer page no: 33 to 35 of the protocol.
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 23
F.1.3 Elderly (>=6
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Previous treatment with Dara-SC.
2. Previous treatment with carfilzomib.
3. Previous treatment with daratumumab within the last 3 months prior to randomization.
4. Discontinuation of Dara-IV due to a daratumumab-related AE.
5. History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further 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.
6. Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, mAbs, human proteins, or their excipients (refer to the IB), or known sensitivity to mammalian derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
7. Contraindications to the use of any components of the backbone treatment regimens, per local prescribing information.
8.1 Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before randomization (except for investigational anti-myeloma
treatments, which cannot be taken within 2 weeks or 5 PK half-lives of the treatment from the date of randomization, whichever is longer)
9. Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study intervention.
10. Plans to father a child while enrolled in this study or within 3 months after the last dose of study intervention.
11. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
12.1. Received anti-myeloma treatment within 2 weeks or 5 PK half-lives of the treatment from the date of randomization, whichever is longer.
The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days; see Appendix 10) up to 21 days before treatment. A list of anti-myeloma
treatments with the corresponding PK half-lives is provided in the Site Investigational Product Procedures Manual.
13. Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing).
14. Plans to undergo a stem cell transplant prior to progression of disease on this study.
For full exclusion criteria, refer page no: 35 to 38 of the protocol.
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