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Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance

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ClinicalTrials.gov Identifier: NCT03311958
Recruitment Status : Recruiting
First Posted : October 17, 2017
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma Drug: Nivolumab, IV, 240 mg Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Regular testing of DLBCL patients who have successfully undergone chemotherapy and are negative for ctDNA. Treatment of patients who become positive for ctDNA with Nivolumab
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance: A Pilot Study in Diffuse Large B-Cell Lymphoma
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : April 15, 2019
Estimated Study Completion Date : April 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Nivolumab Drug: Nivolumab, IV, 240 mg
Patients would be given an infusion of 240 mg nivolumab over 30 min




Primary Outcome Measures :
  1. Evaluation of the rate of conversion from positive to negative ctDNA in nivolumab treated patients [ Time Frame: 2 years ]
    Regular monitoring of ctDNA positive patients on nivolumab until they become ctDNA negative

  2. Evaluation of the rate of conversion from positive to negative ctDNA in nivolumab treated patients [ Time Frame: 2 years ]
    Regular testing of ctDNA in positive patients on nivoluman until clinical relapse


Secondary Outcome Measures :
  1. 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 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

  2. Relapse free survival (RFS-ctDNA) for nivolumab treated patients [ Time Frame: 2 years ]
    RFS will be calculated from the day of nivolumab administration until clinical disease

  3. Proportion of patients who are able to convert from ctDNA positive to ctDNA negative after nivolumab treatment [ Time Frame: 2 years ]
    Number of patients who are ctDNA positive and treated with nivolumab, turn ctDNA negative

  4. To compare the ctDNA results of Clonoseq and Neolabs platform [ Time Frame: 2 years ]
    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



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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03311958


Contacts
Contact: Nadia Khan, MD 215-728-2674 Nadia.Khan@fccc.edu

Locations
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Fox Chase Cancer Center

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT03311958     History of Changes
Other Study ID Numbers: HM-110
First Posted: October 17, 2017    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018

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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs