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

NCT02789228 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 7497
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Incidence of Product-Emergent Adverse Events

  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

  Within 45 days of the last dose of TAA-CT of first infusion and 28 days after the final TAA CTL dose

Secondary Outcomes (1)

• Tumor associated antigen lymphocytes (TAA-CTL) responses

  1 year

Study Arms (2)

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.

Biological: 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.

Biological: Tumor associated antigen lymphocytes (TAA-CTL)

Interventions

Tumor associated antigen lymphocytes (TAA-CTL) BIOLOGICAL

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-T 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

Group A; Group B

Eligibility Criteria

• Age: 6 Months - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Hont AB, Cruz CR, Ulrey R, O'Brien B, Stanojevic M, Datar A, Albihani S, Saunders D, Hanajiri R, Panchapakesan K, Darko S, Banerjee P, Fortiz MF, Hoq F, Lang H, Wang Y, Hanley PJ, Dome JS, Bollard CM, Meany HJ. Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. J Clin Oncol. 2019 Sep 10;37(26):2349-2359. doi: 10.1200/JCO.19.00177. Epub 2019 Jul 29.

  PMID: 31356143 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Hematology-Oncology Fellowship Director

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: June 2, 2016
• Study Start: October 12, 2016
• Primary Completion: April 18, 2022
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)