Inclusion Criteria:
1. Able to understand and voluntarily sign the informed consent form.
2. Aged 18 years or older at the time of signing the informed consent form.
3. Biopsy-proven diagnosis of relapsed classical Hodgkin lymphoma.
4. Measurable disease on imaging defined as at least one lesion that can be accurately
measured in at least two dimensions by imaging (PET/CT, CT or MRI). Minimum
measurement must be ≥ 15mm in the longest axis or ≥ 10mm in the short axis.
5. Relapsed or refractory disease (after at least 2 prior systemic therapies); patients
must have relapsed after high-dose therapy with ASCT, or have been deemed ineligible
for high-dose therapy with ASCT based upon the below criteria:
- Patients that have either progressed after treatment with, be intolerant to, or
are not a candidate for brentuximab and pembrolizumab or nivolumab. The reason
for forgoing such therapies must be clearly documented.
- Are not ASCT candidates due to chemo-resistant disease (unable to achieve CR or
PR to salvage chemotherapy), advanced age (≥ 65 years of age), or any significant
coexisting medical condition (renal, pulmonary, or hepatic dysfunction) likely to
have a negative impact on tolerability of ASCT
6. Disease free of other malignancies for greater than or equal to 2 years with the
exception of basal cell, squamous cell carcinomas of the skin, fully excised melanoma
in situ, carcinoma in situ of the cervix or breast.
7. Performance status of ECOG 0-2 (Appendix 13.3).
8. Laboratory test results within these ranges (of note, patients who have cytopenias due
to documented cHL involvement of the bone marrow may be considered for enrollment
after discussion with the PI, Medical Director and Sponsor):
- Absolute neutrophil count (ANC) > 1,000/µL
- Platelet count > 75,000/µL
- Serum creatinine < 2.0 mg/dL
- Bilirubin < 2.0 × ULN unless bilirubin increase was due to Gilbert's disease.
Further evaluation should be performed to confirm and document the origin of
increase.
- AST and ALT ≤ 2.5 × institutional upper limit of normal (ULN)
- Fasting cholesterol ≤ 300 mg/dL AND fasting triglycerides ≤ 300 mg/dl. NOTE: In
case one or both of these thresholds are exceeded, the patient can only be
included after initiation of appropriate lipid lowering medication prior
initiating study treatment.
9. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotropin (β-hCG) pregnancy test result within 72 hours prior to the
first dose of itacitinib and must agree to use an effective contraception method
during the study and for 6 months following the last dose of study drug; females of
non-childbearing potential are those who are post-menopausal for more than 1 year or
who have had a bilateral tubal ligation or hysterectomy. Female patients undergoing
active fertility preservation therapy/egg harvesting which include hCG injections are
expected to have mild elevation of hCG. These patients may be allowed to participate
in the trial despite elevation of hCG after providing documentation of negative hCG
prior the hCG injection and statement from her fertility specialist that they are not
pregnant.
10. Males who have partners of childbearing potential must agree to use an effective
contraceptive method during the study and for 6 months following the last dose of
study drug.
11. Must be able to comply with the study and follow-up requirements.
12. Subject must have access to everolimus via insurance or self-pay.
Exclusion Criteria:
1. Unable to sign informed consent form.
2. Pregnant or breast-feeding females (lactating females must agree not to breast feed
while taking the investigational agents).
3. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study. For Example:
- symptomatic congestive heart failure of New York Heart Association Class III or
IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within 6 months of start of study drug, serious uncontrolled cardiac
arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function with O2 saturation that is 88% or less at rest on
room air
- active (acute or chronic) or uncontrolled severe infections
- condition requiring ongoing use of medications that are considered STRONG or
MODERATE CYP3A4 inhibitors or inducers and P-gp substrates at study screening .
However, those who require weak inhibitors/inducers can be enroll at discretion
of the PI.
- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
C).
4. Has a history (within the past 12 months) of (non-infectious) pneumonitis requiring
systemic steroids, or active pneumonitis.
5. Bilirubin < 3 × ULN in the presence of liver metastases or presence of documented
Gilbert's syndrome (unconjugated hyperbilirubinemia)
6. Concurrent use of other anti-cancer agents or therapies during study treatment.
7. Use of any other experimental drug or therapy within 28 days of initiating treatment
with the investigational agents.
8. Known seropositive for or active viral infection with human immunodeficiency virus
(HIV), hepatitis C (HCV), or hepatitis B virus (HBV); patients who are seropositive
because of hepatitis B virus vaccine are eligible.
9. Previous use of JAK1 inhibitor (itacitinib), or history of progression on everolimus.
