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B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
3CAR adlı bu Faz 1 (Phase 1) çalışma, 21 yaş ve altındaki, nüks eden veya tedaviye dirençli (relapsed/refractory) B7-H3 pozitif solid tümörü olan hastalarda, hastanın kendi T hücrelerinin B7-H3 hedefli kimerik antijen reseptörü (CAR) taşıyacak şekilde genetik olarak değiştirilmesini incelemektedir. Birincil amaç, lenfositleri azaltan kemoterapi sonrasında tek damar içi B7-H3-CAR T hücre infüzyonunun güvenliğini ve tolere edilebilen en yüksek dozu belirlemektir; ikincil amaç tümöre karşı etkinliğin değerlendirilmesidir. Çalışma müdahaleleri arasında fludarabin (Fludara), siklofosfamid (Cytoxan) ve MESNA (Mesnex) yer almakta; katılım için tümörde B7-H3 ifadesinin standart immünohistokimya ile gösterilmesi ve ölçülebilir hastalık bulunması gerekmektedir.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: Procurement and T-cell production eligibility\* \*a previously collected, autologous leukapheresis product can be used for T-cell production * Age ≤21 years old * B7-H3+ solid tumor with measurable disease; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor is considered B7-H3 positive with an H-score ≥100 * Estimated life expectancy of \>12 weeks * Karnofsky or Lansky (age-dependent) performance score ≥50 * For females of child bearing age: * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment * Not lactating with intent to breastfeed * Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis Exclusion Criteria: * Known primary immunodeficiency * Known HIV positivity * Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection) * History of hypersensitivity reactions to murine protein-containing products * Rapidly progressive disease (in the opinion of the study PIs) Inclusion criteria Treatment eligibility * Age ≤21 years old * B7-H3+ solid tumor with measurable disease * Evidence of relapsed or refractory disease after standard first-line therapy * Estimated life expectancy of \>8 weeks * Karnofsky or Lansky (age-dependent) performance score≥50 * Echocardiogram with a ventricular ejection fraction * \>40%; or shortening fraction ≥25% * Adequate renal function defined as creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age) * Adequate pulmonary function defined as pulse oximetry ≥92% on room air or forced vital capacity (FVC) ≥50% of predicted value * Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age * Hemoglobin≥ 7g/dL (can be transfused) * Platelet count \>50,000/uL (can be transfused) * Absolute neutrophil count (ANC) ≥ 1000/uL * Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy * For females of child bearing age: * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment * Not lactating with intent to breastfeed * If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom. * Available autologous transduced T-cell product that has met GMP release criteria * Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products Exclusion criteria * Known primary immunodeficiency * History of HIV infection * Severe, uncontrolled intercurrent bacterial, viral or fungal infection * History of hypersensitivity reactions to murine protein-containing products * Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion * Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs). * Rapidly progressing disease (in the opinion of the study PIs)