Clinical Trial: NCT02789228 - My Cancer Genome

NCT02789228

Description:

Patients with high-risk solid tumors, those that are refractory to standard up front therapy or relapse after completion of therapy, have a very poor prognosis despite attempts to induce remission with salvage regimen. Novel therapies are critical for this patient population with high-risk cancer. The ability of tumors to be recognized and lysed by the immune system offers a unique opportunity to aid in tumor eradication by expanding and activating these anti-tumor cells. Through this ability to harness sophisticated and specific immunotherapy, residual or relapsed disease that is resistant to chemotherapy and/or radiotherapy could be eradicated. Prior studies have suggested both safety of expanded specific T cells and efficacy in the setting of melanoma, lymphoma or viral eradication. While this therapy has previously been limited by the versatility of the tumor to down-regulate antigens and evade a single immune-target, the use of multi-antigen specific T cells may permit better and more durable anti-tumor immunity. Thus, the investigators propose to infuse these specific multi-antigen anti-tumor T lymphocytes into patients with high risk solid tumors. This trial will be conducted to demonstrate safety of these cells and generate efficacy and biology data that may be important for future studies that may enhance tumor immunotherapy.

Related Conditions:

Adenocarcinoma
Esophageal Carcinoma
Ewing Sarcoma
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Soft Tissue Sarcoma
Wilms Tumor

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02789228

Trial Eligibility

Document

Title

Brief Title: Research Study Utilizing Expanded Multi-antigen Specific Lymphocytes for the Treatment of Solid Tumors
Official Title:

Clinical Trial IDs

ORG STUDY ID: 7497
NCT ID: NCT02789228

Conditions

Solid Tumors

Interventions

Drug	Synonyms	Arms
Tumor associated antigen lymphocytes (TAA-CTL)		Group A

Purpose

Detailed Description

      This protocol is designed as a phase I dose-escalation study. In each treatment group (A and
      B), patients will be enrolled to one of the following TAA-CTL dose levels:

      Dose Level One: 1 x 107 cells/m2 Dose Level Two: 2 x 107 cells/m2 Dose Level Three: 4 x 107
      cells/m2

      Patients will receive cells due to the presence of refractory disease and/or high risk for
      disease relapse and/or residual detectable disease following HSCT or conventional therapy at
      the time of the infusion. Group A and Group B patients will use the dose escalation strategy
      described above. Ideally, patients should not receive other systemic antineoplastic agents
      for at least 45 days after the infusion of TAA- CTL (for purposes of evaluation), although
      such treatment may be added if deemed critical for patient care by the attending physician.

      Two to four patients will be enrolled at each dose level until the maximum tolerated dose
      (MTD) is determined at which point to ensure safety a total 8 patients will be treated at the
      MTD. Each patient will receive at least one TAA-CTL infusion and may receive a maximum of 8
      doses total. Dose escalation will occur once at least 2 patients have completed the 45 day
      follow up period following their first TAA-CTL infusion. The first and second doses will be
      administered 45 days apart then additional doses will be spaced every 28 days. The expected
      volume of each infusion is 1 to 10 cc.

      Expansion cohorts of Group B patients with Wilms tumor, neuroblastoma, rhabdomyosarcoma,
      adenocarcinoma and esophageal cancer will be permitted to enroll up to 6 additional patients
      in each disease group, to be treated at the MTD.

      Within group B, a cohort of patients with relapsed or refractory Wilms tumor will be enrolled
      and receive a lymphodepleting chemotherapy regimen followed by TAA-T.

      If patients with measurable or evaluable disease have a response of stable disease or better
      by RECIST criteria at the day 28 evaluation after dose 2 or subsequent evaluations they are
      eligible to receive up to 6 additional doses of CTLs at 28 day intervals. Each subsequent
      doseis expected to be at the enrollment dose level (i.e. no subsequent dose escalation).
      Following dose 1, if a patient's T cell supply is insufficient for subsequent doses at the
      enrollment dose level, further treatments may be administered at a lower dose level at the
      treating physician's discretion.

Trial Arms

Name	Type	Description	Interventions
Group A	Experimental	Group A includes patients who have undergone an allogeneic hematopoietic stem cell transplant (HSCT) as part of their prior therapy. Group A patients (post allogeneic HSCT): TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first.	Tumor associated antigen lymphocytes (TAA-CTL)
Group B	Experimental	Group B includes patients who have undergone conventional (standard) therapy which does not include an allogeneic HSCT. Within group B, a cohort of patients with relapsed or refractory Wilms tumor will be enrolled and receive a lymphodepleting chemotherapy regimen followed by TAA-T. Group B patients (no prior allogeneic HSCT): TAA-T will be infused any time >1 week after completing most recent course of conventional (non-investigational) therapy for their disease. Patients receiving lymphodepletion will be >2 weeks from most recent course of conventional therapy and have nadired and recovered before beginning protocol therapy.	Tumor associated antigen lymphocytes (TAA-CTL)

Eligibility Criteria

        Inclusion Criteria:

        Recipient procurement inclusion criteria

          -  Diagnosis of high-risk solid tumors: Ewing sarcoma, Wilms tumor, neuroblastoma,
             rhabdomyosarcoma, soft tissue sarcomas, osteosarcoma, adenocarcinoma, and esophageal
             carcinoma and renal cell carcinoma.

          -  Refractory disease, residual detectable disease following conventional therapy or
             relapsed disease.

          -  6 months to 60 years of age at enrollment.*

          -  Karnofsky/Lansky score of ≥ 50%.*

          -  Absolute neutrophil count (ANC) greater than 500/µL. *

          -  Absolute lymphocyte count (ALC) greater than 1000/µL.*

          -  Bilirubin ≤ 2.5 mg/dL. *

          -  Aspartate aminotransferase (AST)/ Alanine transaminase (ALT) ≤ 5x the upper limit of
             normal for age. *

          -  Serum creatinine < 1.0 mg/dL or 2 x the upper limit of normal for age (whichever is
             higher).*

          -  Pulse oximetry of > 90% on room air.*

          -  Agree to use contraceptive measures during study protocol participation (when age
             appropriate).*

          -  LVEF > 50% or LVSF > 27 % if history of total body irradiation (TBI).

          -  Patient or parent/guardian capable of providing informed consent.

        Exclusion Criteria:

        Recipient Procurement exclusion criteria

          -  Patients with uncontrolled infections

          -  Patients with active HIV

          -  Current evidence of GVHD > grade 2 or chronic GVHD manifestations: bronchiolitis
             obliterans syndrome, sclerotic GVHD, or serositis.

          -  Pregnant or lactating females

          -  Prior immunotherapy with an investigational agent within the last 28 days prior to
             procurement

        Recipient Inclusion to administer cells:

          -  Steroids less than 0.5 mg/kg/day prednisone (or equivalent).

          -  Karnofsky/Lansky score of ≥ 50% %.

          -  Bilirubin ≤ 2.5 mg/dL.

          -  AST/ALT ≤ 5x the upper limit of normal for age.

          -  Serum creatinine < 1.0 mg/dL or 2x the upper limit of normal for age (whichever is
             higher).

          -  Pulse oximetry of > 90% on room air.

          -  Patients receiving lymphodepleting chemotherapy must have:

        ANC >750 /uL Platelet count >75,000 /uL

        Recipient Exclusion to administer cells:

          -  Patients with uncontrolled infections

          -  Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal
             antibodies within 28 days prior to TAA-T cell infusion

          -  Acute GVHD > grade 2 or chronic GVHD manifestations: bronchiolitis obliterans
             syndrome, sclerotic GVHD, or serositis

          -  Pregnant or lactating females

Maximum Eligible Age:	60 Years
Minimum Eligible Age:	6 Months
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Incidence of Product-Emergent Adverse Events
Time Frame:	Within 45 days of the last dose of TAA-CT of first infusion and 28 days after the final TAA CTL dose
Safety Issue:
Description:	Primary endpoint of the study is defined grade ≥3 infusion-related adverse event occurring within 45 days of the last TAA-CTL dose, grade ≥4 non-hematologic adverse event occurring within 45 days of the last TAA-CTL dose and that are not due to the patient's underlying malignancy or pre-existing co-morbidities or grade ≥3 acute GVHD occurring within 45 days of the last TAA-CTL dose, or any unexpected toxicity of any grade attributed to the infusion of TAA-CTL occurring within 45 days of the last TAA-CTL dose. Toxicities will be defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03

Secondary Outcome Measures

Measure:	Tumor associated antigen lymphocytes (TAA-CTL) responses
Time Frame:	1 year
Safety Issue:
Description:	o determine the number of patients who respond to tumor associated antigen lymphocytes (TAA-CTL)

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Children's National Research Institute

Last Updated

February 25, 2021

Clinical Trials /

Research Study Utilizing Expanded Multi-antigen Specific Lymphocytes for the Treatment of Solid Tumors