Itacitinib + Everolimus in Hodgkin Lymphoma

NCT03697408 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: IRB # 831774; UPCC #45418
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Classical Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Phase II: Efficacy of Itacitinib in Combination With Everolimus

  Evaluate the efficacy of itacitinib in combination with everolimus in subjects with relapsed or refractory cHL as demonstrated by complete response (CR) rate, defined as the percentage of subjects achieving CR as their best response.

  2 Years

Secondary Outcomes (6)

• Determine the Efficacy of Itacitinib in Combination With Everolimus in Terms of Overall Response Rate (ORR).

  2 years

• Determine the Efficacy of Itacitinib in Combination With Everolimus in Terms of Partial Response (PR).

  2 years

• Determine the Efficacy of Itacitinib in Combination With Everolimus in Terms of Stable Disease (SD).

  2 years

• Determine the Efficacy of Itacitinib in Combination With Everolimus in Terms of Duration of Response.

  2 years

• Determine the Efficacy of Itacitinib in Combination With Everolimus in Terms of Progression Free Survival (PFS).

  2 years

Study Arms (3)

Cohort -1

EXPERIMENTAL

Itacitinib 200 mg once daily (QD) in combination with everolimus 5 mg QD

Drug: Itacitinib; Drug: Everolimus

Cohort 1 (starting dose)

EXPERIMENTAL

Itacitinib 300 mg once daily (QD) in combination with everolimus 5 mg QD

Drug: Itacitinib; Drug: Everolimus

Cohort 2

EXPERIMENTAL

Itacitinib 400 mg once daily (QD) in combination with everolimus 5 mg QD

Drug: Itacitinib; Drug: Everolimus

Interventions

Itacitinib DRUG

A JAK 1 selective small molecule inhibitor

Also known as: INCB039110

Cohort -1; Cohort 1 (starting dose); Cohort 2

Everolimus DRUG

A mammalian target of rapamycin (mTOR) inhibitor

Also known as: Afinitor

Cohort -1; Cohort 1 (starting dose); Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign the informed consent form.
• Aged 18 years or older at the time of signing the informed consent form.
• Biopsy-proven diagnosis of relapsed classical Hodgkin lymphoma.
• 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.
• 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.
• Performance status of ECOG 0-2 (Appendix 13.3).
• 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)

You may not qualify if:

• Unable to sign informed consent form.
• Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking the investigational agents).
• 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).
• Has a history (within the past 12 months) of (non-infectious) pneumonitis requiring systemic steroids, or active pneumonitis.
• Bilirubin \< 3 × ULN in the presence of liver metastases or presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia)
• Concurrent use of other anti-cancer agents or therapies during study treatment.
• Use of any other experimental drug or therapy within 28 days of initiating treatment with the investigational agents.
• 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.
• Previous use of JAK1 inhibitor (itacitinib), or history of progression on everolimus.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

itacitinib; INCB039110; Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Jakub Svoboda, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 5, 2018
• Study Start: February 11, 2019
• Primary Completion: May 20, 2024
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Locations

US (1)