Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

NCT03681561 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BTCRC-HEM15-027
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  To assess the maximum tolerated dose (MTD) of ruxolitinib in combination with nivolumab in patients with relapsed/refractory Hodgkin lymphoma. (Phase I Only)

  24 months

• Overall Disease Control

  To evaluate the best Overall Disease Control (CR+PR+SD) at 3 months of nivolumab in combination with ruxolitinib at MTD in patients with relapsed/refractory Hodgkin lymphoma using the modified Lugano Classification "lymphoma response criteria to immunomodulatory therapy criteria" (LYRIC)1 (Phase II Only)

  24 months

Secondary Outcomes (5)

• Overall Response Rate

  24 months

• Progression Free Survival

  24 months

• Duration of Response

  24 months

• Overall Survival

  24 months

• Frequency and Severity of Adverse Events as assessed by CTCAE v4.0

  24 months

Study Arms (2)

Phase I:Ruxolitinib and Nivolumab

EXPERIMENTAL

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.

Drug: Ruxolitinib; Drug: Nivolumab

Phase II: Ruxolitinib and Nivolumab

EXPERIMENTAL

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.

Drug: Ruxolitinib; Drug: Nivolumab

Interventions

Ruxolitinib 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.

Also known as: Jakafi

Phase I:Ruxolitinib and Nivolumab; Phase II: Ruxolitinib and Nivolumab

Nivolumab DRUG

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

Also known as: Opdivo

Phase I:Ruxolitinib and Nivolumab; Phase II: Ruxolitinib and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, mixed response, or relapse
• Failed at least one prior therapy
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Veronika Bachanova: lead
• Incyte Corporation: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

COMPLETED

Indiana Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

WITHDRAWN

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Hodgkin Disease

Interventions

ruxolitinib; Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Veronkia Bachanova

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veronika Bachanova

CONTACT

612-625-5469; bach0173@umn.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: September 13, 2018
• Primary Completion: March 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)