Daratumumab after Stem Cell Transplant in Treating Patients with Multiple Myeloma

Inclusion Criteria

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Age 18 to 70 years
• Histologically confirmed diagnosis of multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
• Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-13 months of the first dose of initial therapy
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Patients with planned standard of care ASCT using melphalan 200 mg/m^2; dose modifications in accordance with creatinine clearance levels are allowed per physician judgment
• Adequate organ function for high dose chemotherapy and autologous stem cell transplant (as per institution standard operating procedure [SOP])
• Adequate cell dose > 2.5 x 10^6 CD34+ cells/kg
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 75,000/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
• Total bilirubin =< 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =< 3 x ULN
• Alanine aminotransferase (ALT) =< 3 x ULN
• Calculated creatinine clearance >= 30 mL/min
• Woman of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods; condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization; true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (1 year after melphalan and 3 months after the last dose of daratumumab for women) * A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria

• Prior disease progression with daratumumab or other anti-CD38 antibody
• History of organ or previous autologous/allogeneic stem cell transplantation
• Any condition medical or psychosocial that in the opinion of the investigator would hinder compliance
• Female patients who are lactating or have a positive pregnancy test during the screening period
• Evidence of multiple myeloma (MM) disease progression any time prior to enrollment; progression from smoldering to active myeloma is not exclusionary
• History of plasma cell leukemia or central nervous system (CNS) involvement
• Major surgery within 14 days prior to start of study treatment
• Infection requiring systemic antibiotic therapy within 14 days prior to the start of study treatment
• Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment; Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable
• Vaccination with live attenuated vaccines within 4 weeks of first study agent administration
• Subject is currently using or has used immunosuppressive medication within 14 days prior to the first dose of study treatment; the following are exceptions: * Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection) * Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent * Steroids as premedication for hypersensitivity reaction (e.g., infusion-related reactions, computed tomography [CT] scan premedication)
• Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis
• Subjects with uncontrolled, systematic infection should be excluded
• Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% predicted normal; Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50%
• Subject has known moderate or severe persistent asthma within 2 years, or currently has uncontrolled asthma of any classification; (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)
• Subject has active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., Crohn's disease], diverticulitis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment; the following are exceptions: * Subjects with vitiligo or alopecia * Subjects with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement * Psoriasis not requiring systemic treatment
• Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients
• Subject has history of primary immunodeficiency
• Subject is seropositive for human immunodeficiency virus (HIV-1)
• Active hepatitis A
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]); subjects with resolved infection (I.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs] must be screened using real-time polymerase chain reaction [PCR] measurement of hepatitis B virus [HBV] deoxyribonucleic acid [DNA] levels; those who are PCR positive will be excluded); EXCEPTION: Subjects with serologic finding suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
• Subject has any one of the following: * Clinically significant abnormal electrocardiogram (ECG) finding at screening * Congestive heart failure (New York Heart Association class III or IV) * Myocardial infarction within 12 months prior to starting study treatment * Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
• Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for >= 5 years with the exception of the following malignancies: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system) or prostate cancer that is curative
• Any other condition that would, in the opinion of the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)