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.

Conditions

Eligibility

Eligible Ages
Between 12 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
TAA-T with Nivolumab
All 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.
  • Biological: TAA-T cells
    TAA-T cells will be generated from lymphocytes obtained from patient's peripheral blood mononuclear cells (PBMCs). 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: For patients <18 years, 3 mg/kg/dose (maximum 240mg/dose) every 2 weeks. For adult patients ≥18 years, a fixed dose of 240mg every 2 weeks.

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Hema Dave, MD
202-476-6397
HKDave@childrensnational.org

More Details

NCT ID
NCT03843294
Status
Recruiting
Sponsor
Catherine Bollard

Study Contact

Hema Dave, MD
202-476-6397
HKDave@childrensnational.org

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.