Itacitinib and Everolimus in Treating Patients with Relapsed or Refractory Classic Hodgkin Lymphoma

Status: Active

Description

This phase I / II trial studies the side effects and best dose of itacitinib when given together with everolimus in treating patients with classic Hodgkin lymphoma that has come back or does not respond to treatment. Itacitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving itacitinib with everolimus may work better in treating patients with classic Hodgkin lymphoma compared to giving itacitinib or everolimus alone.

Eligibility Criteria

Inclusion Criteria

  • Able to understand and voluntarily sign 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 (positron emission tomography [PET]/computed tomography [CT], CT or magnetic resonance imaging [MRI]). Minimum measurement must be >= 15 mm in the longest axis or >= 10 mm in the short axis
  • Relapsed or refractory disease (after at least 2 prior systemic therapies); patients must have relapsed after high-dose therapy with autologous stem cell transplant (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 Eastern Cooperative Oncology Group (ECOG) 0-2
  • Of note, patients who have cytopenias due to documented cHL involvement of the bone marrow may be considered for enrollment after discussion with the principal investigator [PI], medical director and sponsor)
  • Absolute neutrophil count (ANC) > 1,000/uL
  • Platelet count > 75,000/uL
  • Serum creatinine < 2.0 mg/dL
  • Bilirubin < 2.0 x upper limit of normal (ULN) unless bilirubin increase was due to Gilbert's disease. Further evaluation should be performed to confirm and document the origin of increase
  • Aspartate aminotransferase (AST) and alanine aminotransferase(ALT) =< 2.5 x institutional upper limit of normal (ULN)
  • Fasting cholesterol =< 300 mg/dL AND fasting triglycerides =< 2.5 x ULN. 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
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-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
  • 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
  • Must be able to comply with the study and follow-up requirements
  • Subject must have access to everolimus via insurance or self-pay

Exclusion Criteria

  • 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 as defined as history of diffusion capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (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-glycoprotein (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)
  • Bilirubin < 3 x 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
  • Has a history of (non-infectious) pneumonitis requiring systemic steroids, or active pneumonitis

Locations & Contacts

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Contact: Jakub Svoboda
Phone: 215-614-1846

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. 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 classic Hodgkin lymphoma (cHL). (Phase I)

II. To evaluate the efficacy of itacitinib in combination with everolimus in subjects with relapsed or refractory cHL as demonstrated by complete response (CR) rate. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of itacitinib in combination with everolimus in terms of CR, objective response rate (ORR), partial response (PR), stable disease (SD), duration of response, progression-free survival (PFS), and overall survival (OS). (Phase I)

II. To evaluate efficacy in terms of ORR, PR, SD, duration of response, PFS, OS. (Phase II)

III. To evaluate the safety and tolerability of the treatment combination. (Phase II)

EXPLORATORY OBJECTIVES:

I. To evaluate impact of itacitinib in combination with everolimus on quality of life (QOL). (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of itacitinib, followed by a phase II study.

Patients receive itacitinib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days, then every 3 months for the first year, and every 6 months for the second year.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Jakub Svoboda

Trial IDs

Primary ID UPCC 45418
Secondary IDs NCI-2019-01193
Clinicaltrials.gov ID NCT03697408