Phase I/II Study of Nivolumab in Combination With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Ruxolitinib
- Conditions
- Hodgkin Lymphoma
- Sponsor
- Veronika Bachanova
- Enrollment
- 54
- Locations
- 6
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Recruiting
- Last Updated
- last month
Overview
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).
Investigators
Veronika Bachanova
Sponsor-Investigator
Big Ten Cancer Research Consortium
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
- •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)
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
Arms & Interventions
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.
Intervention: Ruxolitinib
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.
Intervention: Nivolumab
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.
Intervention: Ruxolitinib
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.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: 24 months
To assess the maximum tolerated dose (MTD) of ruxolitinib in combination with nivolumab in patients with relapsed/refractory Hodgkin lymphoma. (Phase I Only)
Overall Disease Control
Time Frame: 24 months
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)
Secondary Outcomes
- 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)