Clinical trial NCT03681561: Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
Official title: Phase I/II Study of Nivolumab in Combination With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hodgkin Lymphoma
Lead sponsor: Big Ten Cancer Research Consortium
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
name: Bristol-Myers Squibb
First posted: 2018-09-24
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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, 1 or 2.
* Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or refractory - historical biopsy at last relapse is acceptable. NOTE: a repeat biopsy is not required for Phase I if the historical biopsy was performed at the most recent relapse, without remission in between. A fresh biopsy is not required for Phase II.
* 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.
* Prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others) and subsequent progressive disease, stable disease or mixed response
* 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. Radiation therapy must be completed at least 7 days prior to registration.
* Absolute Neutrophil Count ≥ 1000/μL
* Platelets ≥ 75,000/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:

* 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
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
* Active Hepatitis B or C infection (defined as a positive Hepatitis B surface antigen (Ag) or detectable viral load by PCR). NOTES: Hepatitis B and C testing is required. Patients with positive Hepatitis B Ag may enroll if PCR is negative. Suppressive antiviral therapy should be considered for these patients as clinically indicated.
* 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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 24 months
measure: Overall Disease Control
timeFrame: 24 months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 24 months
measure: Progression Free Survival
timeFrame: 24 months
measure: Duration of Response
timeFrame: 24 months
measure: Overall Survival
timeFrame: 24 months
measure: Frequency and Severity of Adverse Events as assessed by CTCAE v4.0
timeFrame: 24 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Minnesota
name: Veronkia Bachanova
role: PRINCIPAL_INVESTIGATOR
References: