Phase 2 study of Daratumumab in combination with Thalidomide and Dexamethasone in relapsed or refractory Myeloma
- Conditions
- Diseases of the blood and blood -forming organs and certain disorders involving the immune mechanism
- Registration Number
- KCT0004202
- Lead Sponsor
- Seoul National University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 70
? Multiple myeloma, diagnosed according to standard criteria of International Myeloma Workshop, with relapsing and refractory disease after the last treatment at study entry
? Males and females = 18 years of age
? Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
- Serum M-protein = 0.5g/dL,
- Urine M-protein = 200mg/24 hour,
- In subjects without detectable serum M-protein, Urine M-protein, or serum free light chai = 100mg/L (involved light chain) and an abnormal kappa/Lambda ratio
? Must receive at least 1 line but does not exceed 6th of prior treatment. (Induction therapy followed by stem cell transplantation and consolidation/maintenance therapy will be considered as one line of treatment)
? Must have relapsed disease and/or be refractory to prior treatment except for thalidomide or lenalidomide. Refractoriness is defined as disease progression on treatment or progression within 6 months after the last dose of a given therapy. Relapse is defined according to the criteria of International Myeloma Workshop.
? Eastern Cooperative Oncology Group Performance Status of 0 to 2
? Patients must meet the following clinical laboratory criteria with 21 days of starting treatment.
- Absolute neutrophil count = 1,000/mm3 and platelet = 50,000/mm3 (= 30,000/mm3 if myeloma involvement in the bone marrow is >50%)
- Total bilirubin = 1.5 x the upper limit of the normal range. Alanine aminotransferase and aspartate aminotransferase = 3 x the upper limit of the normal range.
- Calculated or measured on the basis of a standard formula, such as Cockcroft and Gault creatinine clearance = 30mL/minute
? Female patients who:
- Are naturally postmenopausal or surgically sterile for at least 2 year before enrolment
- All female of childbearing potential must have two negative pregnancy test within 10-14 days and 24hrs before commencing thalidomide. Female of childbearing potential must agree to use two reliable methods of contraception simultaneously or practice complete abstinence from any heterosexual intercourse during the following time periods related to this study: for at least 28 days before starting study ; while participating in the study; for at least 28 days after last daratumumab dosing or for 6 months after last thalidomide doging.
? Male patients, even if surgically sterilized (i.e. status post-vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 28 days after the last dose of study treatment and agree to not donate sperm at all the time.
? Written informed consent in accordance with federal, local and institutional guidelines
1) Female patients who are lactating or pregnant
2) Multiple Myeloma of Immunoglobulin M subtype
3) Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 14 days prior to informed consent obtained
4) Polyneuropathy/Organomegaly/Endocrinoapthy/Monoclonal gammopathy or M proteins/Skin defects(POEMS) syndrome
5) Plasma cell leukemia or circulating plasma cells > 2.0 x 109/L
6) Waldenstrom’s Macroglobulinaemia
7) Existing peripheral neuropathy of grade 2 or higher or presence of neuropathic pain within 14 days prior to informed consent obtained
8) Patients with known amyloidosis or myelodysplastic syndrome
9) Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting this study.
10) Focal radiation therapy within 7 days prior to start of this study. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to start of Daratumumab.
11) Patients who have received immunotherapy (except steroids) and biotoxin that are likely to be active within 21 days of the start of treatment for this clinical trial
12) Major surgery (excluding kyphoplasty) within 28 days prior to start of this study.
13) Active congestive heart failure (New York Heart Association Class 3 or 4), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained.
14) Patients to human immunodeficiency virus infection, hepatitis C (acute hepatitis C reaching continuous viral response after antiviral treatment), or active infection requiring antiviral, anti-bacterial agents, including test subjects known as serum-positive (defined as positive examination of hepatitis B surface antigen) for hepatitis B. Subjects with resolved infection (ie, subjects who are hepatitis B surface antigen negative but positive for antibodies to hepatitis B core antigen and/or antibodies to hepatitis B surface antigen) must be screened using realtime polymerase chain reaction measurement of hepatitis B virus deoxyribonucleic acid levels. Those who are polymerase chain reaction positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of hepatitis B virus vaccination (antibodies to hepatitis B surface antigen positivity as the only serologic marker) AND a known history of prior hepatitis B virus vaccination, do not need to be tested for hepatitis B virus deoxyribonucleic acid by polymerase chain reaction.
15) Patients with known arteriosclerosis
16) Patients with creatinine clearance <30mL/minute
17) Second malignancy within the past 3 years except:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Breast carcinoma in situ with full surgical resection
18) Patients with steroid or thalidomide hypersensitivity
19) Patients previously treated with daratumumab or other anti-CD38 antibodies.
20) Ongoing graft-versus-host disease
21) Disease refractory to thalidomide or lenalidomide
22) Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting this study
23) Any clinically significant medical disease or psychiatric condition that, in the investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.
24) Patients with known allergies, overreaction or resistance to monoclonal antibodies, human proteins or their subcom
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method progression free survival
- Secondary Outcome Measures
Name Time Method Overall Response rate;Overall Survival;Duration of response;Safety(adverse events accorging to NCI CTCAE version 4.03 criteria)