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Personalized TIL cellular therapy. Significant in-patient hospital stay (Bethesda, MD). Requires a tumor deemed by the trial MD to be large enough & surgically harvestable.

Clinical paper of MSS-CRC Success: https://www.ncbi.nlm.nih.gov/pubmed/27959684

We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11×1011 HLA-C*08:02–restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex (MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-C*08:02.

Above Patient’s perspective: http://cancerriot.blogspot.com/p/procedures.html

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Criterios de inclusión

* CRITERIOS DE INCLUSIÓN:
* Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial, or endocrine tumors including neuroendocrine tumors. Patients must have at least one lesion that is resectable for TIL generation with minimal morbidity, preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit.
* Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.
* Refractory to approved standard systemic therapy. Specifically:

* Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan.
* Patients with hepatocellular carcinoma must have received sorafenib (Nexavar(R)), since level 1 data support a survival benefit with this agent.
* Patients with breast and ovarian cancer must be refractory to both first- and second-line treatments and must have received at least one second-line chemotherapy regimen.
* Patients with 3 or fewer brain metastases that are < 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. * Age greater than or equal to 18 years and less than or equal to 72 years. * Clinical performance status of ECOG 0 or 1. * Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for individuals of child-bearing potential (IOCBP) and for four months after treatment for individuals that can father children. * IOCBP must have a negative pregnancy test be a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. Serology * Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. Hematology * ANC > 1000/mm^3 sin el apoyo de filgrastim
* WBC mayor o igual a 2500/mm^3
* Recuento de plaquetas mayor o igual a 80.000/mm^3
* Hemoglobina > 8,0 g/dL. Los sujetos pueden ser transfundidos para alcanzar este límite.

Chemistry

* ALT/AST en suero inferior o igual a 5,0 x ULN
* Serum creatinine less than or equal to 1.5 x ULN
* Bilirrubina total menor o igual a 2,0 mg/dL, excepto en pacientes con Síndrome de Gilbert s, que deben tener una bilirrubina total < 3,0 mg/dL.
* Patients must have completed any prior systemic therapy at the time of enrollment.

Nota: Los pacientes pueden haber sido sometidos a intervenciones quirúrgicas menores o a radioterapia de campo limitado en las cuatro semanas previas a la inscripción, siempre que las toxicidades orgánicas importantes relacionadas se hayan recuperado hasta un grado inferior o igual a 1.

* Ability of subject to understand and the willingness to sign a written informed consent document.
* Willing to sign a durable power of attorney.
* Subjects must be co-enrolled on protocol 03-C-0277.

Criterios de exclusión

CRITERIOS DE EXCLUSIÓN:

* Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
* Terapia esteroidea sistémica concurrente.
* Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
* Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion.
* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
* History of major organ autoimmune disease.
* Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1/PD-L1 therapy.
* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
* Antecedentes de reacción de hipersensibilidad inmediata grave a la ciclofosfamida, fludarabina o aldesleukina.
* Antecedentes de revascularización coronaria o síntomas isquémicos.
* For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.
* Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction.
* For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.
* Patients who are receiving any other investigational agents.