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Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT03681561
Recruitment Status : Recruiting
First Posted : September 24, 2018
Last Update Posted : April 12, 2019
Sponsor:
Collaborators:
Incyte Corporation
Bristol-Myers Squibb
Information provided by (Responsible Party):
Veronika Bachanova, Big Ten Cancer Research Consortium

Brief Summary:
This is a Phase I/II, multicenter, open-label, dose escalation/dose-expansion study to evaluate the tolerability, safety, and the maximum tolerated dose (MTD) of ruxolitinib when given with fixed dose nivolumab in patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Drug: Ruxolitinib Drug: Nivolumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Nivolumab in Combination With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
Actual Study Start Date : September 13, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
Experimental: Ruxolitinib and Nivolumab Drug: Ruxolitinib

Ruxolitinib at assigned dose* twice daily by mouth begin Day 1 and continuing daily until study treatment stop.

Dose Levels:

1 (starting) : 10mg twice daily 2: 15mg twice daily 3: 20mg: twice daily

Other Name: Jakafi

Drug: Nivolumab
Nivolumab 480 mg IV every 4 weeks (Day 1) Until disease progression, unacceptable toxicity, patient refusal or a maximum of 2 years




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 24 months ]
    To assess the maximum tolerated dose (MTD) of ruxolitinib in combination with nivolumab in patients with relapsed/refractory Hodgkin lymphoma.


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 24 months ]
    To evaluate the best overall response rate (ORR) of nivolumab in combination with ruxolitinib in patients with relapsed/refractory Hodgkin lymphoma using the modified Lugano Classification "lymphoma response criteria to immunomodulatory therapy criteria" (LYRIC).

  2. Progression Free Survival [ Time Frame: 24 months ]
    To evaluate progression free survival (PFS) at 2 years for nivolumab in combination with ruxolitinib in patients with relapsed/refractory Hodgkin lymphoma using the modified Lugano Classification "lymphoma response criteria to immunomodulatory therapy criteria" (LYRIC)

  3. Duration of Response [ Time Frame: 24 months ]
    To evaluate duration of response (DOR) at 2 years for nivolumab in combination with ruxolitinib in patients with relapsed/refractory Hodgkin lymphoma using the modified Lugano Classification "lymphoma response criteria to immunomodulatory therapy criteria" (LYRIC)

  4. Overall Survival [ Time Frame: 24 months ]
    To evaluate overall survival (OS) at 2 years for nivolumab in combination with ruxolitinib in patients with relapsed/refractory Hodgkin lymphoma using the modified Lugano Classification "lymphoma response criteria to immunomodulatory therapy criteria" (LYRIC)

  5. Frequency and Severity of Adverse Events as assessed by CTCAE v4.0 [ Time Frame: 24 months ]
    To characterize he safety and tolerability of nivolumab in combination with ruxolitinib as determined by the frequency and severity of adverse events (AEs) as defined by the NCI's Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)



Information from the National Library of Medicine

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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:

  • Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0 or 1.
  • Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or refractory - historical biopsy at last relapse is acceptable.
  • Presence of radiographically measurable disease (defined as the presence one or more ≥ 1.5 cm lesions, as measured in the longest dimension by PET/CT) within 4 weeks of study registration.
  • Failed prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others)
  • Failed at least 2 prior therapies including cytotoxic chemotherapy including ABVD or similar, autologous transplantation, brentuximab vedotin, allogenic transplantation without active graft versus host disease Note: Patients who are eligible and willing to undergo autologous transplant should not be enrolled on this trial
  • Prior cancer treatment must be completed at least 14 days prior to registration and the patient must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
  • Absolute Neutrophil Count ≥ 1000/μL
  • Platelets ≥ 100,000/μL (or ≥50,000/mm3 if known BM involvement)
  • Calculated creatinine clearance ≥ 40 cc/min using the Cockcroft-Gault formula
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Males who are sexually active with partners of child-bearing potential must be willing to abstain from heterosexual activity or adhere to contraception from the time of written consent until 7 months after treatment discontinuation.
  • Patient must provide voluntary written informed consent prior to the performance of any research related tests or procedures.

Exclusion Criteria:

  • Prior exposure to ruxolitinib
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Inability or unwillingness to swallow oral medication or any condition that precludes the administration and/or absorption of oral medications
  • A life-threatening illness, medical condition or organ system dysfunction, which in the investigator's opinion, could compromise the patient's safety, interfere with the metabolism of study drugs, or put the study outcomes at undue risk
  • Active central nervous system (CNS) involvement by lymphoma
  • Uncontrolled cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Concomitant therapy with immunosuppressive agents, including systemic corticosteroids (doses ≤ 10 mg/day prednisone or equivalent are permitted).
  • Has a history of autoimmune disease now or in past 3 years such as hepatitis, nephritis, hyperthyroidism, interstitial lung disease or colitis except vitiligo or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
  • History of HIV infection. NOTE: HIV testing is required.
  • Active Hepatitis B or C infection (defined as a positive Hepatitis B surface antigen or detectable viral load by PCR). NOTE: Hepatitis B and C testing is required.
  • Currently active, clinically significant hepatic impairment Child-Pugh class B or C
  • Currently receiving a strong CYP3A4 Inhibitor (such as but not limited to boceprevir clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) or Fluconazole >200 mg/day. Washout period of 1 week is required.
  • History of stroke or intracranial hemorrhage within 6 months of study registration

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): NCT03681561


Contacts
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Contact: Veronika Bachanova 6126255469 bach0173@umn.edu
Contact: Donna Sullivan 3179212050 dsullivan@hoosiercancer.org

Locations
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United States, Illinois
University of Illinois Cancer Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Alana Aziz-Bradley    312-996-2088    aaziz6@uic.edu   
Principal Investigator: David Peace, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Marian Anderson    319-353-4578    marian-andersen@uiowa.edu   
Principal Investigator: Umar Faroog, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Erin Zielinski    612-624-0937    eezielin@umn.edu   
Principal Investigator: Veronika Bachanova, MD         
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53705
Contact: Kaitlin Chambers    608-263-5006    kchambers2@wisc.edu   
Principal Investigator: Vaishalee Kenkre, MD         
Sponsors and Collaborators
Veronika Bachanova
Incyte Corporation
Bristol-Myers Squibb

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Responsible Party: Veronika Bachanova, Sponsor-Investigator, Big Ten Cancer Research Consortium
ClinicalTrials.gov Identifier: NCT03681561     History of Changes
Other Study ID Numbers: BTCRC-HEM15-027
First Posted: September 24, 2018    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents