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Trial record 51 of 1216 for:    "Hodgkin lymphoma"

Itacitinib + Everolimus in Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT03697408
Recruitment Status : Recruiting
First Posted : October 5, 2018
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

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).

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Drug: Itacitinib Drug: Everolimus Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 11, 2019
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2027


Arm Intervention/treatment
Experimental: Itacitinib and everolimus Drug: Itacitinib
A JAK 1 selective small molecule inhibitor
Other Name: INCB039110

Drug: Everolimus
A mammalian target of rapamycin (mTOR) inhibitor
Other Name: Afinitor




Primary Outcome Measures :
  1. Phase I: Collection of dose-limiting toxicities of combination treatment with itacitinib and everolimus. [ Time Frame: 30 Days ]
    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.

  2. Phase II: Efficacy of itacitinib in combination with everolimus [ Time Frame: 2 Years ]
    Evaluate the efficacy of itacitinib in combination with everolimus in subjects with relapsed or refractory cHL as demonstrated by complete response (CR) rate


Secondary Outcome Measures :
  1. Determine the efficacy of itacitinib in combination with everolimus in terms of Complete Response (CR). [ Time Frame: 2 years ]
  2. Determine the efficacy of itacitinib in combination with everolimus in terms of Overall Response Rate (ORR). [ Time Frame: 2 years ]
  3. Determine the efficacy of itacitinib in combination with everolimus in terms of Partial Response (PR). [ Time Frame: 2 years ]
  4. Determine the efficacy of itacitinib in combination with everolimus in terms of Stable Disease (SD). [ Time Frame: 2 years ]
  5. Determine the efficacy of itacitinib in combination with everolimus in terms of duration of response. [ Time Frame: 2 years ]
  6. Determine the efficacy of itacitinib in combination with everolimus in terms of progression free survival (PFS). [ Time Frame: 2 years ]
  7. Determine the efficacy of itacitinib in combination with everolimus in terms of overall survival (OS). [ Time Frame: 2 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≤ 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.
  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 as defined as history of DLCO that is 50% of the normal predicted value and/or 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.
  9. Has a history of (non-infectious) pneumonitis requiring systemic steroids, or active pneumonitis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03697408


Contacts
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Contact: Abramson Cancer Center of the University of Pennsylvania 215-615-5858 Terese.Waite@uphs.upenn.edu

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Terease Waite, RN       Terese.Waite@uphs.upenn.edu   
Contact: Tanya Latorre, RN       Tanya.Latorre@uphs.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Jakub Svoboda, MD University of Pennsylvania

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03697408     History of Changes
Other Study ID Numbers: IRB # 831774; UPCC #45418
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents