Clinical Trials /

Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance

NCT03311958

Description:

Patients suffering from diffuse large B-cell lymphoma (DLBCL) who relapse within 12 months of chemotherapy usually undergo salvage therapies, followed by autologous transplant with a low success rate. These treatments for relapse have significant toxicities and may not be tolerated well by the patients. These patients need an effective means of identifying relapse at an early time point to be treated effectively. Detection of circulating tumor DNA (ctDNA) has been reported to be a sensitive and more specific method to detect relapse at an early stage compared to PET/ CT scans. Purpose of this trial is to monitor patients who have undergone successful chemotherapy for the presence of ctDNA. Patients who test positive for ctDNA would be treated with Nivolumab for a period of 2 years to avoid complete relapse.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance
  • Official Title: Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance: A Pilot Study in Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: HM-110
  • NCT ID: NCT03311958

Conditions

  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
Nivolumab, IV, 240 mgNivolumab

Purpose

Patients suffering from diffuse large B-cell lymphoma (DLBCL) who relapse within 12 months of chemotherapy usually undergo salvage therapies, followed by autologous transplant with a low success rate. These treatments for relapse have significant toxicities and may not be tolerated well by the patients. These patients need an effective means of identifying relapse at an early time point to be treated effectively. Detection of circulating tumor DNA (ctDNA) has been reported to be a sensitive and more specific method to detect relapse at an early stage compared to PET/ CT scans. Purpose of this trial is to monitor patients who have undergone successful chemotherapy for the presence of ctDNA. Patients who test positive for ctDNA would be treated with Nivolumab for a period of 2 years to avoid complete relapse.

Detailed Description

      Primary Objective:

      To determine if nivolumab administration, as a maintenance strategy in DLBCL patients with
      high risk of relapse, can convert positive ctDNA to negative ctDNA and/or result in relapse
      free survival (RFS-ctDNA) of 9 months or longer after positive ctDNA was documented.

      Secondary Objectives:

        1. To evaluate safety of nivolumab as maintenance drug in post-induction, post-salvage and
           post-autologous transplant setting

        2. Relapse free survival (RFS-ctDNA) for nivolumab treated patients

        3. Proportion of patients who are able to convert from ctDNA positive to ctDNA negative
           after nivolumab treatment

        4. To validate NeoLabs assay platform by comparing the results to Clonoseq platform.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimental
  • Nivolumab, IV, 240 mg

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a tissue diagnosis of diffuse large B cell lymphoma, with a
             negative PET/CT scan performed within 28 days of study enrollment, with one of the
             following clinical features: high risk IPI, ABC-subtype DLBCL, Double hit/ triple hit
             DLBCL, Ki67>90%, or MYC translocation.

          -  Patients can have any number of prior therapies and any amount of time period from the
             last therapy as long as they have complete response as seen in PET/CT at the time of
             enrolment.

          -  Patients with prior salvage chemo-immunotherapy, radiation therapy, autologous
             transplantation are included

          -  Prior radiation therapy must be completed at least 2 weeks prior to study enrollment

          -  Autologous transplant must have been done 100 days prior to the study enrollment

          -  Age > 18 years.

          -  ECOG performance status ≤ 2

          -  Life expectancy of at least 3 months

          -  A formalin fixed tissue block or equivalent of 24 slides of the tumor sample for
             analyses by Adaptive Sequenta and NeoGenomics must be available for analysis.

          -  Patients must be off cancer-directed therapy for at least 3 weeks (2 weeks for oral
             agents prior to day 1 of the study

          -  Patients must have suitable organ and marrow function as defined below

               -  Absolute neutrophil count > 500/mm3

               -  Platelets > 20,000/mm3

               -  Total bilirubin < 2.5 times the ULN

               -  AST/ALT (SGOT/SGPT) < 2 times institutional normal limits

               -  Creatinine ≤1.5 times normal institutional limits OR

               -  Creatinine clearance > 40 ml/min for patients

          -  Ability to understand and willingness to sign a written informed consent and HIPAA
             consent document

          -  WOCBP and sexually active, non-sterile men must be willing to use acceptable method of
             contraception. WOCBP must agree to not get pregnant and sexually active, non-sterile
             men must agree not to impregnate a woman for at least 18 weeks after the last dose of
             nivolumab

        Exclusion Criteria:

          -  Patients with second malignancies (except monoclonal B cells of undetermined
             significance, antecendant indolent non Hodgkin lymphoma, non-melanomatous skin
             cancers, papillary thyroid carcinomas, ductal carcinoma in-situ, superficial bladder
             cancer, prostate cancer or in situ cervical cancers) are excluded unless a complete
             remission was achieved at least 3 years prior to enrollment and no additional therapy
             is required or anticipated to be required during the treatment.

          -  Subjects with active autoimmune disease or a syndrome that requires systemic
             corticosteroids

          -  Subjects who received non-oncology vaccine therapies for prevention of infectious
             disease within 4 weeks of study drug administration.

          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent

          -  Any contraindication to therapy with nivolumab

          -  Prior allogeneic transplantation

          -  Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with
             documented cure from HCV infection will be included

          -  Known uncontrolled human immunodeficiency virus (HIV) infection or known acquired
             immunodeficiency syndrome (AIDS). Patients with documented controlled HIV infection
             (CD4 > 200 and undetectable viral load) will be included.

          -  Any condition requiring systemic treatment with corticosteroids (> 10 mg daily
             prednisone or equivalent) or other immunosuppressive medications within 14 days prior
             to first dose of study drug. Inhaled or topical steroids and adrenal replacement
             steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of
             active autoimmune disease.

          -  History of anaphylactic reaction to monoclonal antibody therapy

          -  Poor psychiatric risk

          -  Patients receiving other investigational agents

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant or breast feeding. Refer to section 4.4 for further details
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluation of the rate of conversion from positive to negative ctDNA in nivolumab treated patients
Time Frame:2 years
Safety Issue:
Description:Regular monitoring of ctDNA positive patients on nivolumab until they become ctDNA negative

Secondary Outcome Measures

Measure:To evaluate adverse events in patients on nivolumab as maintenance drug in post-induction, post-salvage and post-autologous transplant setting
Time Frame:2 years
Safety Issue:
Description:Safety evaluated by the frequency and grade of adverse events, as defined by NCI CTCAE 4.03 criteria, for patients treated with nivolumab, such as, uveitis, abnormal lab report or intercurrent illness
Measure:Relapse free survival (RFS-ctDNA) for nivolumab treated patients
Time Frame:2 years
Safety Issue:
Description:RFS will be calculated from the day of nivolumab administration until clinical disease
Measure:Proportion of patients who are able to convert from ctDNA positive to ctDNA negative after nivolumab treatment
Time Frame:2 years
Safety Issue:
Description:Number of patients who are ctDNA positive and treated with nivolumab, turn ctDNA negative
Measure:To compare the ctDNA results of Clonoseq and Neolabs platform
Time Frame:2 years
Safety Issue:
Description:The results obtained from the two platforms will be compared for the feasibility of NeoLabs platform for detecting any change in ctDNA numbers in blood

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

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