Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30) (ANCILE-30)
This Phase I study will evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes modified to express a constitutively active IL7 receptor (C7R) and a chimeric antigen receptor (CAR) for CD30 (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas.
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of the investigational product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by infusion of autologous C7R.CD30-CAR-EBVSTs.
The primary objective is to evaluate safety. Secondary and exploratory objectives include evaluation of antitumor effect, expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
This is a Phase I study to evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes (EBVSTs) genetically modified to express a constitutively active interleukin-7 receptor (C7R) and a CD30-specific chimeric antigen receptor (CAR) (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas. The study will also evaluate the antitumor effect of C7R.CD30-CAR-EBVSTs, the expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.
Autologous CD30 CAR T cells have demonstrated clinical activity in patients with relapsed or refractory CD30-positive lymphomas but have shown limited persistence. Epstein-Barr virus-specific T lymphocytes (EBVSTs) have demonstrated long-term persistence following adoptive transfer. In this study, EBVSTs are used as the cellular platform to express both a CD30 CAR and a constitutively active IL7 receptor (C7R). The investigational cell product also provides a mechanism for rapid elimination of transduced cells if clinically indicated.
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of an autologous C7R.CD30-CAR-EBVST product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of C7R.CD30-CAR-EBVSTs. Participants who meet retreatment criteria, as defined in the protocol, may receive additional treatment cycles. Following treatment, participants will undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status.
Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy.
Participants are followed longitudinally for up to 15 years after the most recent infusion.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- 1. fázis
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Premal Lulla, MD
- Telefonszám: 713-441-1450
- E-mail: lulla@bcm.edu
Tanulmányi helyek
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Texas
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Houston, Texas, Egyesült Államok, 77030
- Houston Methodist Hospital
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Kapcsolatba lépni:
- Premal Lulla, MD
- Telefonszám: 713-441-1450
- E-mail: lulla@bcm.edu
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
- Gyermek
- Felnőtt
- Idősebb felnőtt
Egészséges önkénteseket fogad
Leírás
Procurement Inclusion Criteria:
Participants must meet the protocol-defined procurement eligibility criteria before collection of peripheral blood mononuclear cells for manufacture of the investigational product, including:
- Diagnosis of relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma.
- CD30 positive tumor (can be pending at this time) as assayed in a CLIA certified Pathology Laboratory.
- Age 16 to 75 years.
- Hemoglobin ≥7.0(may be transfused value).
- Karnofsky or Lansky score of > 60%
- Informed consent explained to, understood by and signed by patient or guardian. Patient or guardian given copy of informed consent.
Procurement Exclusion Criteria:
- Active HIV or HTLV infection (testing may be pending at procurement).
Active bacterial, fungal, or viral infection.
____________________________________________________________________________
Treatment Inclusion Criteria:
Participants with a successfully manufactured product must continue to satisfy the protocol-defined treatment eligibility criteria before receiving study treatment, including:
Diagnosis and clinical course falling into one of the following categories:
- Hodgkin lymphoma
- CD30+ aggressive B-cell lymphoma
- ALK-negative anaplastic T cell lymphoma or other peripheral T- cell lymphoma
- ALK-positive anaplastic T cell lymphoma
- CD30 expression confirmed in a CLIA-certified laboratory. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy
- Age 16 to 75 years.
- Bilirubin ≤ 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be Bilirubin ≤ 3 times the upper limit of normal).
- AST ˂ 3 times the upper limit of normal
- Estimated GFR > 50 mL/min
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after study is concluded. Male partner should use a condom
- Informed consent explained to, understood by and signed by patient/guardian. Patient/Guardian given copy of informed consent.
Treatment Exclusion Criteria:
- Received an investigational cell therapy or vaccine within the past 6 weeks.
- Received an investigational small molecule within the past 2 weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products
- Pregnancy or breastfeeding.
- Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion)
- Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
- Active significant, uncontrolled bacterial, viral or fungal infection.
- Symptomatic cardiac disease (NYHA Class III or IV disease).
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Kísérleti: Autologous C7R.CD30-CAR-EBVSTs
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of autologous C7R.CD30-CAR-EBVSTs.
Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of autologous C7R.CD30-CAR-EBVSTs.
Participants who meet protocol-defined retreatment criteria may receive additional treatment cycles.
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Autologous Epstein-Barr virus-specific T lymphocytes genetically modified to express a constitutively active interleukin-7 receptor (C7R), a CD30-specific chimeric antigen receptor (CAR), and an inducible caspase 9 (iC9) safety switch.
The investigational product is manufactured from autologous peripheral blood mononuclear cells and administered by intravenous infusion following lymphodepleting chemotherapy.
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Incidence of Dose-Limiting Toxicities (DLTs)
Időkeret: From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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Dose-limiting toxicity (DLT) is defined as any of the following considered possibly, probably, or definitely related to study cellular products: (1) Grade 5 event without disease progression; (2) CRS: Grade 4, or Grade 3 not improving to ≤Grade 2 within 72 hours despite therapy; (3) ICANS: Grade 4, or Grade 3 not improving within 72 hours despite therapy; (4) Grade ≥3 IEC-HS; (5) Grade 4 neutropenia or thrombocytopenia not attributable to underlying disease or lymphodepleting chemotherapy and not improving to ≤Grade 2 within 42 days, or Grade 3 thrombocytopenia with clinically significant major bleeding; (6) Grade ≥3 vital organ toxicity (except transient hepatic or renal abnormalities improving to ≤Grade 2 within 7 days); (7) other Grade 3 toxicities not attributable to underlying disease or lymphodepleting chemotherapy and not resolving to ≤Grade 2 within 72 hours; (8) Grade ≥2 allergic reaction to T-cell infusion.
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From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Antitumor Effect
Időkeret: 4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
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Antitumor effect will be assessed by investigator evaluation of objective response (complete response and partial response) using Lugano criteria.[
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4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
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Együttműködők és nyomozók
Együttműködők
Nyomozók
- Kutatásvezető: Helen Heslop, MD, The Methodist Hospital Research Institute
- Kutatásvezető: Premal Lulla, MD, The Methodist Hospital Research Institute
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
- Neoplazmák
- Immunrendszeri betegségek
- Neoplazmák szövettani típus szerint
- Nyirokrendszeri betegségek
- Limfoproliferatív rendellenességek
- Immunproliferatív rendellenességek
- Limfóma, non-Hodgkin
- Limfóma, B-sejt
- Limfóma
- Limfóma, T-sejt
- Hemikus és nyirokbetegségek
- Limfóma, nagy B-sejtes, diffúz
- Hodgkin-kór
- Limfóma, T-sejt, Perifériás
- Limfóma, nagysejtes, anaplasztikus
Egyéb vizsgálati azonosító számok
- ANCILE-30
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
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az Egyesült Államokban gyártott és onnan exportált termék
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