Clinical Trials /

Itacitinib + Everolimus in Hodgkin Lymphoma

NCT03697408

Description:

This is an open-label, single-group, Phase I/II study of itacitinib in combination with everolimus in subjects with relapsed or refractory classical Hodgkin lymphoma (cHL).

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Itacitinib + Everolimus in Hodgkin Lymphoma
  • Official Title: An Open-Label Phase I/II Safety and Efficacy Study of Itacitinib In Combination With Everolimus In Subjects With Relapsed/Refractory Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IRB # 831774; UPCC #45418
  • NCT ID: NCT03697408

Conditions

  • Classical Hodgkin Lymphoma

Interventions

DrugSynonymsArms
ItacitinibINCB039110Itacitinib and everolimus
EverolimusAfinitorItacitinib and everolimus

Purpose

This is an open-label, single-group, Phase I/II study of itacitinib in combination with everolimus in subjects with relapsed or refractory classical Hodgkin lymphoma (cHL).

Trial Arms

NameTypeDescriptionInterventions
Itacitinib and everolimusExperimental
  • Itacitinib
  • Everolimus

Eligibility Criteria

        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

               -  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.

          6. Performance status of ECOG 0-2 (Appendix 13.3).

          7. 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.

          8. Females of childbearing potential must have a negative serum or urine beta human
             chorionic gonadotropin (β-hCG) pregnancy test result within 7 days 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.

          9. 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.

         10. Must be able to comply with the study and follow-up requirements.

         11. 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. Bilirubin < 3 × ULN in the presence of liver metastases or presence of documented
             Gilbert's syndrome (unconjugated hyperbilirubinemia)

          5. Concurrent use of other anti-cancer agents or therapies during study treatment.

          6. Use of any other experimental drug or therapy within 28 days of initiating treatment
             with the investigational agents.

          7. 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.

          8. Previous use of JAK1 inhibitor (itacitinib), or history of progression on everolimus.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Collection of dose-limiting toxicities of combination treatment with itacitinib and everolimus.
Time Frame:30 Days
Safety Issue:
Description:To evaluate dose-limiting toxicities (DLTs) of combination treatment with itacitinib and everolimus occurring up to and during Day 28 of Cycle 1, and to establish a recommended Phase II dose (RP2D) in subjects with relapsed or refractory cHL.

Secondary Outcome Measures

Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of Complete Response (CR).
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of Overall Response Rate (ORR).
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of Partial Response (PR).
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of Stable Disease (SD).
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of duration of response.
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of progression free survival (PFS).
Time Frame:2 years
Safety Issue:
Description:
Measure:Determine the efficacy of itacitinib in combination with everolimus in terms of overall survival (OS).
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

July 25, 2019