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Clinical Trial 21060
Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03220022
Phase: N/A
Principal Investigator: Sandoval-Sus, Jose
Overview
Study Title
A Pilot Study of Ibrutinib and R-da-EPOCH for Front Line Treatment of AIDS-Related Lymphomas
Summary
This study is currently being conducted at Moffitt's Memorial Healthcare site in Hollywood, Florida. This study is to assess the safety and tolerability of ibrutinib and R-da-EPOCH in patients with Aids-Related Lymphomas.
Objective
To assess the safety and tolerability of ibrutinib and R-da-EPOCH in participants with ARL. This will define the recommended phase II dose (RP2D) of ibrutinib in combination with R-da-EPOCH in participants with ARL.
Treatments
Therapies
Medications
Inclusion Criteria
Age 18-64 Participants must have histologically (via at least a core or ideally, incisional or excisional biopsy) documented CD20 positive or negative diffuse large B-cell lymphoma (DLBCL). Tissue available from the diagnostic biopsy in the form of blocks, tissue cores, or slides available for submission to central pathology is required for all participants enrolled to this study. Stage II-IV disease. Participant will need measurable disease by CT or PET scans if enrolled in the dose-expansion cohort. HIV positive For the dose-finding cohort participants lymphoma must be untreated. For the dose-expansion cohort participants may have either untreated lymphoma or may have received prior therapy. Please see the exclusion criteria for full details of chemotherapy participants may have received off study. ECOG performance status 50% For the dose-finding cohort participants must have a CD4 count ≥ 100 cells/mm3. For the dose-expansion cohort participants may have any CD4 count, including a CD4 count > Participants must have organ and marrow function within the parameters noted in the protocol. Participants must not be on medications, including ARV regimens such as cobicistat, indinavir, or ritonavir, or agents with moderate or strong CYP3A4 inhibition; if on a moderate or strong CYP3A4 inhibitor regimen prior to study enrollment, participants must be switched to a qualifying regimen with the last dose of the strong CYP3A4 inhibitor taken at least one week before administration of ibrutinib. Sexually active participants must be willing to use adequate contraception as outlined in the protocol. All participants are required to be screened for Hepatitis B. All participants who present with acute hepatitis B or show normal transaminases and are HBsAg+ and IgM+ for Hepatitis core antigen will not be eligible for trial enrollment. Per IDSA
and AASD guidelines, those participants that show no immunity, defined by the lack of Hepatitis B surface antibody, and show evidence of chronic infection (i.e. HBsAg+, HBcore+, HBsAB-) will be required to be on anti-Hepatitis B therapy, during the study, in order to be eligible. The exact Hepatitis B therapy will be at the discretion of the infection disease specialist or investigator. If infected with Hepatitis B, participants will be permitted to enroll in the study provided liver function tests meet criteria listed above, there is no evidence of cirrhosis AND participants will be required to be on anti-Hepatitis B therapy. All participants will be required to be screened for Hepatitis C. If Hepatitis C antibody positive, with or without a positive Hepatitis C RNA level, participants will be permitted to enroll in the study provided liver function tests meet criteria listed, and have no evidence of cirrhosis. Participants diagnosed with Hepatitis C less than 6 months from trial enrollment will be considered to have acute Hepatitis C, and will be excluded from study UNLESS Hepatitis C viral load is undetectable Adequate cardiac function defined as an ejection fraction on ECHO or MUGA that is at or above the institutional normal amounts.For the dose-expansion cohort, if the participant had a pre-treatment ECHO prior to pre-study therapy which reports adequate cardiac function defined as an ejection fraction on ECHO or MUGA that is at or above the institutional normal limits, a repeat ECHO will not need to be repeated prior to start of study treatment. Must be able to swallow oral pills Other criteria may apply
Inclusion Criteria:
Exclusion Criteria
Participants who have had chemotherapy other than R-EPOCH, R-CHOP or limited therapy as outlined in Section 3.2.2, or radiotherapy other than palliative radiation for medical emergencies (like cord compression), within the last 4 weeks. For the dose-finding cohort prior cytotoxic chemotherapy or radiotherapy for this lymphoma is exclusionary. For the dose-expansion cohort participants may have received: (a) A maximum of one cycle of combination chemotherapy, including rituximab-containing regimens R-CHOP and R-EPOCH. The start of previous chemotherapy cycle must occur at least 21 days but no more than 28 days prior to beginning treatment 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). OR (b) 1 prior cycle of limited therapy including cyclophosphamide and/or rituximab and/or glucocorticoids to improve hepatic or renal function
impaired due to lymphoma involvement. The start of this therapy may occur up to 28 days prior to beginning treatment under this protocol; cyclophosphamide administration must have been completed at least 14 days prior to initiation of protocol therapy. Such treatment will not count towards the maximum of 6 cycles under this study (i.e., participants will receive 6 cycles on study). For the dose-finding cohort rituximab within 12 months prior to study registration will be exclusionary; only exception will be if rituximab was given for indications other than the treatment of aggressive lymphoma. For the dose-expansion cohort one cycle of rituximab as part of R-CHOP or R- EPOCH or limited therapy as outlined in Section 3.2.2 may be administered off study prior to enrollment; prior rituximab will also be allowed if rituximab was given for indications other than the treatment of aggressive lymphoma Participants who are receiving any other investigational agents Participants who have previously received ibrutinib for another indication. Expected survival under 2 months Participants with a history of an opportunistic fungal infection or active fungal infection requiring, or at high risk of requiring, prophylactic or treatment with fluconazole, voriconazole or posaconazole. Participants with known brain metastases from solid tumors should 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. Presence of second active tumor, other than non-melanoma skin cancer, carcinoma in situ of the cervix, or Kaposi’s sarcoma (KS) that requires systemic therapy. For the dose-finding cohort participants with known or suspected parenchymal brain, spinal cord, leptomeningeal disease prior to study enrollment will be excluded. For the dose-expansion cohort participants with known or suspected parenchymal
brain or spinal cord disease, or symptomatic leptomeningeal disease will be excluded. Asymptomatic leptomeningeal disease will be allowed. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or other agents used in study. 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, in the opinion of the investigator, would limit compliance with study requirements. Pregnancy or breastfeeding. A pregnancy test must be performed within 7 days prior to ibrutinib initiation in women of childbearing potential. Breastfeeding must be discontinued because of unknown but potential risks in the nursing infant Other exclusions apply
Exclusion Criteria:
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