A Pilot/Feasibility Trial of 64Cu-DOTA-Daratumumab Positron Emission Tomography in Patients With Newly Diagnosed or Relapsed Multiple Myeloma
A Pilot/Feasibility Trial of 64Cu-DOTA-Daratumumab Positron Emission Tomography in Patients With Newly Diagnosed or Relapsed Multiple Myeloma
This pilot phase I clinical trial studies how well copper 64Cu-DOTA-daratumumab positron emission tomography works in diagnosing patients with multiple myeloma that has come back. Diagnostic procedures, such as copper 64Cu-DOTA-daratumumab positron emission tomography, may help evaluate the extent of multiple myeloma in patients prior to the initiation of treatment and ultimately monitor disease status/response during and post treatment.
PRIMARY OBJECTIVES:
I. To assess safety and tolerability of unlabeled daratumumab followed by 64Cu-DOTA-daratumumab positron emission tomography, at each dose level, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.
SECONDARY OBJECTIVES:
I. Generate initial estimates of the biodistribution of the 64Cu-DOTA-daratumumab and the preferred dose of cold antibody.
II. Determine the dose of pre-administered unlabeled daratumumab that optimizes image quality of 64Cu-anti-CD38 (daratumumab)-NHS-DOTA.
III. Evaluate the sensitivity of 64Cu-anti-CD38 (daratumumab)-NHS-DOTA in detecting lesions compared to 18F fludeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning.
OUTLINE:
Patients receive daratumumab intravenously (IV) over 10-45 minutes, and within 6 hours, patients receive copper 64Cu-DOTA-daratumumab IV on day 0. Patients undergo PET on days 1 and 2.
After completion of study, patients are followed up for 7 days and then at 2 weeks.
Inclusion Criteria:
All subjects must have the ability to understand and the willingness to sign a written informed consent
Histologically confirmed multiple myeloma (newly diagnosed or relapsed)(Note: multiple myeloma patients with secondary amyloidosis are eligible)
Ability to undergo standard PET imaging; an 18 F FDG PET/CT scan will take place within 3 months of enrollment
Karnofsky performance status > 70%
Absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 50/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)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 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 (6 months after the last dose of 64 Cu-anti-CD38 [daratumumab]-NHS-DOTA for women)
Exclusion Criteria:
Daratumumab or other anti CD38 antibody treatment within 3 months prior to study enrollment
Female patients who are lactating or have a positive pregnancy test during the screening period
Major surgery within 14 days prior to start of study treatment
Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment
Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment; subject is receiving bone marrow stimulatory factors (e.g., granulocyte-macrophage colony-stimulating factor [GM-CSF]); 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 study agent administration
Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration; the following are exceptions:
Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis
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 allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure)
Subject has history of primary immunodeficiency
Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B, or active hepatitis A or C
Subject has any one of the following:
Subject has presence of other active malignancy (see exceptions below) (However, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible). The following malignancies are exceptions to the active malignancy statement:
Any other condition that would, in the investigator's judgment, 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)