Clinical Trials /

Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

NCT03681561

Description:

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).

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
  • Official Title: Phase I Study of Nivolumab in Combination With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-HEM15-027
  • NCT ID: NCT03681561

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
RuxolitinibJakafiRuxolitinib and Nivolumab
NivolumabRuxolitinib and Nivolumab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Ruxolitinib and NivolumabExperimental
  • Ruxolitinib
  • Nivolumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:24 months
Safety Issue:
Description:To assess the maximum tolerated dose (MTD) of ruxolitinib in combination with nivolumab in patients with relapsed/refractory Hodgkin lymphoma.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:24 months
Safety Issue:
Description: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).
Measure:Progression Free Survival
Time Frame:24 months
Safety Issue:
Description: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)
Measure:Duration of Response
Time Frame:24 months
Safety Issue:
Description: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)
Measure:Overall Survival
Time Frame:24 months
Safety Issue:
Description: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)
Measure:Frequency and Severity of Adverse Events as assessed by CTCAE v4.0
Time Frame:24 months
Safety Issue:
Description: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)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Veronika Bachanova

Last Updated

April 11, 2019