A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma

Exclusion Criteria

• •1. Prior cytotoxic chemotherapy or radiotherapy for this lymphoma other than palliative radiation for medical emergencies (like cord compression) or the following chemotherapy:
• •• A maximum of one cycle of combination chemotherapy, including EPOCH or CHOP-like therapy. The start of the previous chemotherapy cycle must occur at least 21 days but no more than 28 days prior to the beginning of therapy under this protocol, and such cycle will count towards the maximum of 6 cycles under this study (i.e., cycle off study will count as cycle 1 in terms of feasibility determination as per primary endpoint).
• •OR
• •• One prior cycle of limited therapy including cyclophosphamide and/or glucocorticoids to improve performance status or hepatic or renal function impaired due to lymphoma involvement. The start of this therapy may occur up to 28 days prior to the beginning of study treatment under this protocol. Cyclophosphamide administration must have been completed at least 14 days prior to initiation of study treatment. Such treatment will not count towards the maximum of 6 cycles under this study (i.e., participants will receive 6 cycles on study).
• •2. Patients who are receiving any other investigational agents.
• •3. Participants must not have had previous anthracycline treatment within the last two years, except for liposomal doxorubicin. Any prior exposure to liposomal doxorubicin is allowed as long as the LVEF is ≥45%. It is at the discretion of the investigator if prior exposure to doxorubicin is acceptable.
• •4. Participants who have previously received daratumumab for another indication.
• •5. Participants must not be on cobicistat, indinavir, or ritonavir, or agents that are strong CYP3A4 inhibitors. If on a strong CYP3A4 inhibitor regimen prior to study enrollment, participants must be switched to alternative drugs at least one week prior to administration of study therapy.
• •6. Participants with peripheral neuropathy grade ≥ 3 or neuropathic pain grade ≥ 2.
• •7. Expected survival \< 2 months.
• •8. Participants with known brain metastases from solid tumors will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• •9. Patients with known or suspected parenchymal brain or spinal cord disease, and/or suspected or symptomatic leptomeningeal disease from lymphoma, prior to study enrolled will be excluded. Asymptomatic leptomeningeal disease only will be allowed.
• •10. Patients who are seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). All participants will be required to be screened for Hepatitis B. Participants with resolved infection (i.e., participants 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 HBV DNA levels. Participants who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings 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.
• •11. Patients diagnosed with Hepatitis C who are Hepatitis C antibody positive, whether Hepatitis C RNA level is measurable or not, must have no evidence of cirrhosis and have liver function tests.
• •12. History of allergic reactions, hypersensitivity, or intolerance attributed to compounds of similar chemical or biologic composition to daratumumab, or other agents used in the study or known sensitivity to mammalian-derived products.
• •13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• •14. Pregnancy or breastfeeding. A pregnancy test must be performed within 7 days prior to therapy administration in women of childbearing potential. Pregnant women are excluded from this study because the effects of daratumumab on the developing human fetus are unknown. Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with daratumumab, breastfeeding should be discontinued if the mother is treated with daratumumab. These potential risks may also apply to other agents used in this study. Both male and female participants must use effective methods of birth control during the course of the study and for 3 months after stopping daratumumab. Participants must also agree to not donate eggs or sperm while taking daratumumab and for 3 months after stopping.
• •15. Unable to comply with the requirements of the protocol, or unable to provide adequate informed consent in the opinion of the Principal Investigator.
• •16. Serious, ongoing, non-malignant disease or infection, which in the opinion of the investigator and/or the sponsor would compromise other protocol objectives. Participants with active opportunistic infections are ineligible.
• •17. Major surgery, other than diagnostic surgery, occurring 4 weeks prior to study entry. Splenectomy will not be considered an exclusionary major surgery.
• •18. Myocardial infarction (MI) within 6 months prior to study entry, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
• •19. Either of the following:
• •* Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) is \<50% of predicted normal. Note that FEV1 testing also is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is \<50% of predicted normal.
• •* Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.)
• •20. Participants with prior malignancies are ineligible unless:
• •* Treatment for the prior malignancy was completed at least 2 years prior to the lymphoma treatment start date and the participant has no evidence of the concurrent malignancy OR
• •* The concurrent malignancy is clinically stable and does not require tumor-directed treatment.