Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

Official title:

Phase I/II Study of Nivolumab in Combination With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03681561
• Other study ID #: BTCRC-HEM15-027
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 13, 2018
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Big Ten Cancer Research Consortium
• Contact: Veronika Bachanova
• Phone: 612-625-5469
• Email: bach0173[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Ruxolitinib
Phase I: Ruxolitinib at assigned dose* twice daily by mouth begin Day 1 and continuing daily until study treatment stop. Dose Levels: (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
Nivolumab 480 mg IV every 4 weeks (Day 1) Until disease progression, unacceptable toxicity, patient refusal or a maximum of 2 years

Locations

Country	Name	City	State
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Indiana Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Veronika Bachanova	Bristol-Myers Squibb, Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall Response Rate	To characterize the Best Overall Response Rate (CR+PR) at 6 months of nivolumab in combination with ruxolitinib in patients with relapsed/refractory classical Hodgkin lymphoma (cHL).	24 months
Secondary	Progression Free Survival	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)	24 months
Secondary	Duration of Response	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)	24 months
Secondary	Overall Survival	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)	24 months
Secondary	Frequency and Severity of Adverse Events as assessed by CTCAE v4.0	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)	24 months