Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

NCT ID: NCT03681561

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-13
• Study Completion Date: 2027-07-31

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).

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I:Ruxolitinib and Nivolumab

Participants will receive ruxolitinib at their assigned dose taken orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks (i.e. on Day 1 of a 28-day cycle) until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Phase I: 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

Phase II: Ruxolitinib 20mg twice daily by mouth begin Day 1 and continuing daily until study treatment stop.

Nivolumab

Intervention Type: DRUG

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

Phase II: Ruxolitinib and Nivolumab

Participants will receive ruxolitinib at 20mg orally twice daily on a 28-day cycle combined with nivolumab 480 mg IV administered every 4 weeks (i.e. on Day 1 of a 28-day cycle) until disease progression, unacceptable toxicity, or for a maximum of 2 years.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Phase I: 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

Phase II: Ruxolitinib 20mg twice daily by mouth begin Day 1 and continuing daily until study treatment stop.

Nivolumab

Intervention Type: DRUG

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

Interventions

Ruxolitinib

Phase I: 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

Phase II: Ruxolitinib 20mg twice daily by mouth begin Day 1 and continuing daily until study treatment stop.

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Other Intervention Names

Jakafi; Opdivo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Veronika Bachanova

OTHER

Sponsor Role: lead

Responsible Party

Veronika Bachanova

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Veronkia Bachanova

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status: COMPLETED

Indiana Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status: WITHDRAWN

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status: RECRUITING

University of Wisconsin

Madison, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Veronika Bachanova

Role: CONTACT

bach0173@umn.edu

612-625-5469

Ahran Lee

Role: CONTACT

alee@hoosiercancer.org

317-634-5842 ext. 14

Facility Contacts

Erin Zielinski

Role: primary

eezielin@umn.edu

612-624-0937

Protocol Implementation Coordinator

Role: primary

CTO.Implementation@osumc.edu

614-293-3717

Kaitlin Chambers

Role: primary

kchambers2@wisc.edu

608-263-5006

Other Identifiers

BTCRC-HEM15-027

Identifier Type: -

Identifier Source: org_study_id