Clinical Trials /

Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma

NCT03843294

Description:

This is a Phase I, open-label multi-site trial designed to evaluate the safety and feasibility of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B). The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma
  • Official Title: Phase I Study Utilizing Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor Nivolumab for Relapsed/Refractory Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: SUSTAIN
  • NCT ID: NCT03843294

Conditions

  • Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
TAA-T cellsTAA-T with Nivolumab

Purpose

This is a Phase I, open-label multi-site trial designed to evaluate the safety and feasibility of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B). The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.

Detailed Description

      The investigators will collect blood from the patients to isolate peripheral blood
      mononuclear cells. The investigators will then make special cells called dendritic cells to
      stimulate the T cells. Then they will add special mixtures of tumor proteins WT1, PRAME and
      Survivin and provide a cytokine milieu favorable to T cell expansion/activation, inducing
      selective expansion of T cells targeted to kill tumor cells. This process trains the T cells
      to recognize the tumor proteins and become specialized TAA-T cells. The cells will be grown
      and frozen until ready for us.

      While the T cells are growing, the patients will receive 4 doses of Nivolumab given every 2
      weeks. Patients will then receive two infusions of the TAA-T cells every two weeks and
      monitored for side effects. Patients will not receive any Nivolumab during the 45 days safety
      monitoring period from the first infusion. They will then receive additional two doses of
      Nivolumab following second TAA-T cell infusion on Days 108 and 122 from starting treatment.

      Only group A patients are eligible for additional doses (3 to 8) if they have stable disease
      or response, do not have ≥ grade 3 toxicity attributed to TAA-T cells and do not have
      clinical evidence of rapidly progressing disease requiring urgent therapy.

      This study will first enroll 6 patients total (Groups A and B) in the initial safety
      monitoring or DLT group prior to the expansion phase (additional 12 patients in the expansion
      cohort). After the initial safety phase is complete, additional 12 patients will be enrolled
      to maximum 18 patients.

      For Group B Patients (post auto-HSCT): Study treatment will begin any time after neutrophil
      engraftment or Day 30 post auto-HSCT whichever comes first.

      Both TAA-T cells and Nivolumab will be given at fixed dose with allowed dose de-escalation of
      both agents as follows:

      TAA-T cell dose: 2 x 107 cells/m2 Nivolumab 3 mg/kg/dose every 2 weeks

      From the first 2 enrolled patients, if at least one patient meets dose limiting toxicity
      criteria at the above mentioned combination dose level, then the next 2 patients will receive
      TAA-T cells at 1 x 107 cells/m2 without a change in nivolumab dose. If toxicity criteria are
      met by at least one patient from these 2 patients, then the dose of Nivolumab will be reduced
      to 1mg/kg/dose for patients <18 years or 100 mg for adults <18 years for next 2 patients and
      T cells will be given at the same de-escalated dose of 1x 107 cells/m2.

      If patient meets eligibility criteria for TAA-T cell infusion, the patient (Group A or Group
      B) will receive two TAA-T cell infusions given 2 weeks apart, where the expected volume of
      infusion is 1 to 10 cc.

      In case the patient experiences toxicity from nivolumab prior to the first TAA-T cell
      infusion, they can receive the TAA-T cells after resolution of the Nivolumab toxicities and
      steroid dosing has been reduced less than 0.5mg/kg/day.
    

Trial Arms

NameTypeDescriptionInterventions
TAA-T with NivolumabExperimentalAll patients will receive Nivolumab(3mg/kg) starting on Day 0 every 2 weeks for 4 doses followed by two infusions of Tumor Associated Antigen Specific T cells (TAA-T) given 2 weeks apart. Patients will receive two additional doses of Nivolumab(Day 108 and Day 122) after the safety monitoring period is complete. Patients can continue Nivolumab after Day 136 at the discretion of the referring/treating physician.
  • TAA-T cells

Eligibility Criteria

        Group A (patients with measurable disease) Relapsed/Refractory Hodgkin Lymphoma (HL) and
        Diffuse Large B cell Lymphoma (DLBCL) DLBCL

          -  Patients with Primary Treatment Failure (PTF) and one or more Ultra-high risk (UHR)
             features, no prior salvage treatment required. Please refer to Appendix A for
             definitions of PTF and UHR

          -  Rel/ref DLBCL failing 1st salvage treatment (Progressive disease (PD)/ Stable Disease
             (SD)/Partial Response (PR))

          -  Rel/ref DLBCL without acceptable treatment options in the opinion of the treating
             physician HL

          -  Rel/ref HL failing ≥ 1 salvage regimens, including prior Brentuximab Vedotin (BV)

          -  Rel/ref after autologous HSCT

        Group B (consolidation after auto-HSCT for patients at high risk for relapse) DLBCL

          -  Patients with < CMR/CR (by PET/CT) with initial treatment regimen

          -  Patients with relapse <12 months from diagnosis or <6 months from completion of
             initial therapy

          -  Patients with <CMR/CR (by PET/CT) prior to autologous HSCT

          -  Patients requiring >1 salvage regimen prior to autologous HSCT HL Patients not
             eligible for post auto-HSCT consolidation with Brentuximab AND

          -  Relapsed <12 months from diagnosis or <6 months from completion of initial therapy

          -  Patients with <CMR/CR (by PET/CT) prior to autologous HSCT

          -  Patients requiring >1 salvage regimen prior to autologous HSCT

        Recipient Procurement (TAA-T Cell Generation) Inclusion Criteria

          -  Age 12 years to 80 years

          -  Karnofsky/Lansky score of ≥ 50 (see appendix C).

          -  Agree to use contraceptive measures during study protocol participation (when age
             appropriate)

          -  Patient or parent/guardian capable of providing informed consent

        Recipient Procurement (TAA-T Cell Generation) Exclusion Criteria

          -  Prior allogeneic BMT

          -  Prior solid organ transplant

          -  Patient who has received ATG, Campath or other immunosuppressive T cell monoclonal
             antibodies within 28 days of screening for enrollment

          -  Patient with uncontrolled infections

          -  Patient with active HIV

          -  Pregnancy or lactating

          -  Failure to meet institutional guidelines for treatment with Nivolumab

        Recipient Inclusion Criteria for Initial and Subsequent TAA-T Cell Infusion

          -  Age 12 years to 80 years

          -  Patient has received at least 4 doses of Nivolumab

          -  All toxicities attributed to Nivolumab have resolved Steroids less than 0.5 mg/kg/day
             prednisone or equivalent

          -  Karnofsky/Lansky score of ≥ 50

          -  Pulse oximetry of > 90% on room air

          -  Bilirubin ≤ 2.5 mg/dL, AST/ALT ≤ 5x upper limit of normal, serum creatinine < 1.0 or
             2x the upper limit of normal (whichever is higher)

          -  Absolute neutrophil count > 250/µL (may be supported with GCSF)

          -  Agree to use contraceptive measures during study protocol participation (when age
             appropriate)

          -  Patient or parent/guardian capable of providing informed consent

        Recipient Exclusion Criteria for Initial and Subsequent TAA-T Cell Infusion

          -  Investigational therapies within the last 28 days

          -  Uncontrolled infections
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Product-Emergent Adverse Events
Time Frame:45 days from the first TAA-T cell administrations
Safety Issue:
Description:Number of participants with grades 3-5 infusion-related and grades 4-5 non-hematological adverse events that are not due to the original malignancy, or pre-existing co-morbidities within 45 days of the first dose of TAA-T infusion as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03, change from baseline at day 45.

Secondary Outcome Measures

Measure:Tumor response to combination immunotherapy
Time Frame:1 year
Safety Issue:
Description:Number of patients with tumor associated antigen lymphocytes (TAA-T) with Nivolumab response, change from baseline at year one. Response will be assessed by imaging using the Lugano criteria. Response is defined as any patient who does not progress on this study, including patients with active disease who achieve Complete Metabolic Response (CMR)/Complete Response (CR), Partial Metabolic Response (PMR)/ Partial Response (PR), or No Metabolic Response(NMR)/Stable Disease (SD) by PET/CT.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Catherine Bollard

Last Updated

September 19, 2019