Nivolumab Maintenance Therapy After Autologous Stem Cell Transplant in Hodgkin Lymphoma Pts at Relapse/Progression Risk

• ClinicalTrials.gov Identifier: NCT03436862
• Recruitment Status: Active, not recruiting
• First Posted: February 19, 2018
• Last Update Posted: May 17, 2022
• Sponsor: SCRI Development Innovations, LLC
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

Study Description

Brief Summary:

This is a Phase II single-arm open-label study of nivolumab as maintenance therapy after autologous stem cell transplantation in patients with Hodgkin lymphoma at risk of relapse or progression.

Condition or disease	Intervention/treatment	Phase
Hodgkin Lymphoma	Drug: Nivolumab	Phase 2

Detailed Description:

The primary objective of this study is to evaluate safety and tolerability of nivolumab as maintenance therapy early after autologous stem cell transplant in patients with Hodgkin's Lymphoma (HL).

Eligible patients will receive nivolumab (240 mg IV) every 2 weeks (± 2 days as long as interval between doses is 12-16 days) starting 45-120 post-transplant for up to a maximum of 6 months of treatment. Response to treatment will be assessed 6 months and 1 year post-transplant using Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Single Arm Study of Nivolumab as Maintenance Therapy After Autologous Stem Cell Transplantation in Patients With Hodgkin Lymphoma at Risk of Relapse or Progression
• Actual Study Start Date: May 23, 2018
• Actual Primary Completion Date: May 5, 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab; Patients will receive Nivolumab 240 mg by intravenous infusion (IV) starting Day 45-120 post-transplant (±10 days) every 2 weeks for up to a maximum of 6 months of treatment.	Drug: Nivolumab; Nivolumab 240 mg IV infusion over 60 minutes given every 2 weeks for up to 6 months.; Other Name: Opdivo

Outcome Measures

Primary Outcome Measures :

1. The incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) to evaluate safety and tolerability of nivolumab as maintenance therapy [ Time Frame: Up to 6 months ]
   The reported incidence of AEs and SAEs with an onset on or after the initiation of therapy will be graded according to National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE).

Secondary Outcome Measures :

1. Progression-free survival (PFS) for Nivolumab Maintenance Therapy [ Time Frame: 1 year after date of first dose of study drug for each patient ]
   Kaplan-Meier PFS estimate at 12 month interval when nivolumab is administered as maintenance therapy. Progression-Free Survival (PFS), defined as the time from the first day of study drug administration (Day 1) to disease progression as defined by the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification (Cheson et al. 2014), or death on study. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients 18 years of age and older with Hodgkin Lymphoma who have received auto-HSCT in the previous 45-120 days.
• Complete response (CR), partial response (PR) or stable disease (SD) to salvage therapy prior to ASCT.

• High risk of residual HL post-ASCT, as determined by 1 of the following:

  • Positive positron emission tomography (PET) scan defined by the Deauville scale 3-4 and within 2 months of start of high dose chemotherapy prior to ASCT
  • Refractory to frontline therapy
  • Relapse <12 months after frontline therapy
  • Relapse ≥12 months after frontline therapy with extra-nodal disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 1.

• Adequate hematologic function defined as all of the following:

  • Absolute neutrophil count (ANC) ≥1000/μL
  • Hemoglobin (Hgb) ≥8 g/dL (transfusions to reach this point are not permitted)
  • Platelets ≥50,000/μL (transfusion is not permitted)

• Adequate liver function defined as all of the following:

  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
  • Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin)
• Adequate renal function defined as serum creatinine ≤1.5 mg/dL (133 μmol/L).
• Females of childbearing potential must have a negative serum or urine pregnancy test result within 72 hours prior to the first dose of nivolumab and must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab and for 7 months following their last dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
• Male patients with female partners of childbearing potential and women patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 7 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 7 months following last dose of study drug.

Exclusion Criteria:

• Patients that have received an allogenic transplant.
• Post-ASCT or current therapy with other anti-neoplastic or investigational agents.
• Best clinical response of progressive disease prior to ASCT.
• Patients with any autoimmune disease or a history of autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Use of a study drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to the first dose of nivolumab. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of nivolumab is required.
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
• Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
• Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
• Pregnant or lactating
• Acute or chronic liver, renal, or pancreatic disease.
• Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they require only oral hypoglycemic agents.

• Any of the following cardiac diseases currently or within the last 6 months:

  • Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO)
  • QTc interval >480 ms on screening electrocardiogram (ECG)
  • Unstable angina pectoris
  • Congestive heart failure (New York Heart Association (NYHA) ≥ Grade 2
  • Acute myocardial infarction
  • Conduction abnormality not controlled with pacemaker or medication
  • Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
  • Valvular disease with significant compromise in cardiac function
• Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment).
• Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. Testing at baseline is not required.
• Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Contacts and Locations

Locations

United States, Colorado

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

United States, Missouri

HCA Midwest

Kansas City, Missouri, United States, 64132

United States, Tennessee

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

St. David's South Austin Medical Center

Austin, Texas, United States, 78704

Texas Transplant Institute

San Antonio, Texas, United States, 78229

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

SCRI Development Innovations, LLC

Bristol-Myers Squibb

Investigators

• Study Chair: Carlos Bachier, MD; SCRI Development Innovations, LLC

More Information

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT03436862
• Other Study ID Numbers: SCRI BMT 24
• First Posted: February 19, 2018
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by SCRI Development Innovations, LLC:

Nivolumab; Autologous Stem Cell Transplant; Blood cancers

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action