A Phase I/II Study of Subcutaneous Daratumumab Administration in the Anterior Upper Thigh Vs Abdomen in Patients With Plasma Cell Disorders
The purpose of this study is to look at the safety, tolerability, and serum concentration of daratumumab administered subcutaneously in the thigh versus the abdomen in patients with plasma cell disorders. Daratumumab is a monoclonal antibody that can attach itself to the CD38 protein on the surface of abnormal plasma cells. Daratumumab can kill the abnormal plasma cells and/or help your immune system find and destroy them. Due to the way daratumumab works, normal cells may also be affected. All reference to the words study drug in this consent form will mean Daratumumab. Daratumumab has been approved by the U.S. Food and Drug Administration (FDA) alone or in combination with other standard of care drugs for treatment of multiple myeloma in both subcutaneous (DARZALEX FASPRO®) and intravenous (DARZALEX®) ways of being delivered. The FDA has also approved the subcutaneous administration of daratumumab combined with other standard of care drugs for patients with light chain (AL) amyloidosis. Subcutaneous means the drug is given by an injection just beneath the skin. Intravenous (IV) means the drug is given as an injection directly into a vein. Usually when given subcutaneously, the study drug is given by an injection in the abdomen. Having the drug given by subcutaneous injection (underneath the skin of the abdomen) has lessened the IV related side effects and the drug administration by injection is quicker. However, some patients cannot receive the study drug injections in their abdomen because they find them very painful or have other medical reasons making it difficult to get these injections. The goal of this study is to see if getting the study drug subcutaneously, injected under the skin by a needle, in the patient's upper thigh will have the same results, or better results, as getting the injection in the abdomen. This would therefore, improve patients access to the drug and provide an alternative place to receive the injection of the drug. This study will take place at University of Maryland Medical Center and there will be about 30 people who will take place in this study here. Dr. Badros is the Sponsor-Investigator of the study. Funding to conduct the study and study drug are being provided by Johnson \& Johnson Innovative Medicine (J\&J IM).
• Histologically confirmed diagnosis of MM (newly diagnosed or relapsed) or AL amyloid with planned therapy with daratumumab-based regimen. and has not received daratumumab previously or has received daratumumab \> 6 months prior to planned Cycle 1 Day 1 alone or in combination with other regimens per investigator discretion.
• Provide signed written informed consent
• 18 years or older (at the time consent is obtained)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Participants with a history of autologous stem cell transplant or prior CAR-T cell therapy can enroll on the study provided that:
∙ Therapy was \>100 days prior to study enrollment
‣ No active infection(s)
• Adequate organ system function
• Female participants: Contraceptive use for those participating in clinical studies (men or women) should be consistent with local regulations: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
∙ Is not a woman of childbearing potential (WOCBP) OR
‣ Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency, during the intervention period and for at least 12 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
⁃ A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
• We will review the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a new undetected pregnancy.
• Non childbearing potential is defined as follows (by other than medical reasons):
⁃ ≥45 years of age and has not had menses for \>1 year
⁃ Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range
⁃ Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
• Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
• a. Refrain from donating sperm PLUS either:
⁃ Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
⁃ Must agree to use contraception/barrier and use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year when having sexual intercourse with a woman of childbearing potential
• All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0) must be ≤ Grade 1 at the time of enrollment except for alopecia and Grade 2 peripheral neuropathy.
⁃ Participants are able to comply with visit schedule and agree to weekly visits for 9 weeks