A clinical study to compare the safety, effectiveness and pharmacokinetics (the way the body absorbs, distributes, and gets rid of a drug) of Daratumumab given through the subcutaneous route versus the active monitoring in patients with high risk smoldering multiple myeloma (precancerous form of blood cancer in the bone marrow)

Phase 1

Conditions: Precancerous form of blood cancer in the bone marrow
MedDRA version: 21.0Level: LLTClassification code: 10028228Term: Multiple myeloma Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-507143-11-00

Lead Sponsor: Janssen - Cilag International

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 336

Inclusion Criteria

1. At least 18 years of age or at least the legal age of consent in the jurisdiction in which the study is taking place, whichever is the older age., 10. Willing and able to adhere to the prohibitions and restrictions specified in the protocol., 2. Diagnosis of SMM for =5 years with measurable disease, defined as serum M protein =10 grams per litre (g/L) or urine M protein =200 milligrams (mg)/24 hours or involved serum free light chain (FLC) =100 milligrams per litre (mg/L) and abnormal serum FLC ratio., 3. Bone marrow plasma cells (BMPCs) =10%; and At least 1 of the following; a. Serum M protein =30 g/L, b. Immunoglobulin A (IgA) SMM, c. Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes, d. Serum involved: uninvolved FLC ratio =8 and < 100, or e. Clonal BMPCs >50% to <60% with measurable disease., 4. Eastern cooperative oncology group (ECOG) performance status score of 0 or 1., 5. Pretreatment clinical laboratory values: refer to protocol, 6. Must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study., 7. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 1 method highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants], or partner's vasectomy). Contraception must begin 4 weeks prior to dosing. Highly effective contraception is indicated even where there has been a history of infertility, unless due to hysterectomy., 8. A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization., 9. During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.

Exclusion Criteria

1. Multiple myeloma, requiring treatment, defined by any of the following: a. Bone lesions (one or more osteolytic lesions on low-dose whole body computed tomography [LDCT], positron-emission tomography with computed tomography [PET-CT] or computed tomography [CT]) b. Hypercalcemia (serum calcium >0.25 mmol/L [>1 mg/dL] higher than ULN or >2.75 mmol/L [>11 mg/dL]) c. Renal insufficiency, preferably determined by creatinine clearance <40 mL/min measured or estimated using the modification of diet in renal disease (MDRD), or serum creatinine >177 micro mole per litre (µmol/L) d. Anemia, defined as hemoglobin <10 gram per deci litre (g/dL) or >2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted e. Clonal BMPC percentage =60% f. Serum FLC ratio (involved:uninvolved) =100 (The involved FLC must be =100 mg/L) g. More than 1 focal lesion =5 mm in diameter by magnetic resonance imaging (MRI), 10. Vaccination with live attenuated vaccines within 4 weeks of first study agent administration, 11. Pregnant, breast-feeding, or planning to become pregnant while receiving study treatment or within 3 months after the last dose of daratumumab, 12. Plans to father a child while receiving study treatment or within 3 months after the last dose of daratumumab, 13. Major surgery (requiring general anesthesia or presence of other factors that determines surgery to be considered major) within 2 weeks before randomization or who have not fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of daratumumab. Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate. If there is a question whether a procedure is considered a major surgery, then the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a subject in the study., 14. Known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder). 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 the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Subject is taking any prohibited medications, 2. Primary systemic (immunoglobulin light chain) amyloidosis (AL), 3. Exposure to any of the following a. Prior exposure to daratumumab or prior exposure to other anti-CD38 therapies b. Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate as indicated for osteoporosis is acceptable. c. Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1 d. Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization; or >280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization, 4. Received treatment for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squam