- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01416974
Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab
9. januar 2019 opdateret af: Memorial Sloan Kettering Cancer Center
A Phase I Trial of Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab
The purpose of this Phase I study is to test the safety and effect of specially prepared cells collected from the patients called "modified T cells."
We want to find a safe dose of modified T cells for patients who have disease remaining after initial chemotherapy.
We also want to find out what effects these T cells have on you and your leukemia.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
13
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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New York
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New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering Cancer Center
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- CLL patients with evidence of residual disease, who have achieved PR, nPR or CR with detectable MRD following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab.
- The presence of MRD will be assessed by the flow cytometry and polymerasechain reaction at the MSKCC Diagnostic Molecular Pathology Laboratory.
- Age ≥ 18 years of age.
- Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.
- Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.
Exclusion Criteria:
- Karnofsky performance status <70.
- Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
- Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan.
- Patients previously treated with allogeneic bone marrow or stem cell transplantation are ineligible.
- Patients who are immediate candidates for allogeneic bone marrow or stem cell transplantation. Patients who refuse this option remain eligible and need to be documented as such in patient medical record.
- CLL patients with transformed disease (Richter's transformation) are ineligible for enrollment on this study.
- Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction ≤6 months prior to enrollment
- History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- History of severe non-ischemic cardiomyopathy with EF ≤20%
- Patients with HIV and active hepatitis B or hepatitis C infection are ineligible.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation, with the exception of squamous and basal cell carcinoma of skin.
STEP 2 REGISTRATION (Treatment):
The following additional criteria must be met in order for a patient to be eligible to receive the modified T cell infusion. These labs are to be obtained within 2 weeks of T cell infusion.
- Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: consolidative therapy with autologous T cells genetically
A phase I trial of consolidation therapy with autologous T cells genetically targeted to the B cell specific antigen CD19 for patients with chronic lymphocytic leukemia following upfront chemotherapy with pentostatin, cyclophosphamide and rituximab.
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Patients will first receive a single infusion of therapy conditioning with cyclophosphamide.
followed by consolidative therapy with the modified T cells in 3 planned cohorts.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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toxicity
Tidsramme: 2 years
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Criteria for toxicity: Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
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2 years
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maximum tolerated dose (MTD)
Tidsramme: 2 years
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If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT) then the next dose level will be studied in another cohort of 3 patients
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2 years
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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disease response
Tidsramme: 2 years
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The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow.
Radiographic studies are not required but those that were abnormal pre-treatment will be repeated to document the degree of maximal response.
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2 years
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change in cellular and cytokine tumor microenvironment
Tidsramme: 2 years
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Cellular tumor microenvironment analysis: The presence of regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), as well as the presence of immune effector cells including dendritic cells, NK cells, and effector T cells will be assessed by fluorescence-activated cell sorting (FACS).
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2 years
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the impact of infused modified T cells
Tidsramme: 2 years
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Persistence of gene-modified T cells is defined by the presence of any percentage of detectable cells.
The percentage of gene-modified T cells/ total T cells will be recorded for all patients treated at each dose level.
In addition, gene-modified T cells will be measured daily for two days, weekly for eight weeks and monthly for six months (by FACS and RT-PCR).
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2 years
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
22. august 2011
Primær færdiggørelse (Faktiske)
7. januar 2019
Studieafslutning (Faktiske)
7. januar 2019
Datoer for studieregistrering
Først indsendt
12. august 2011
Først indsendt, der opfyldte QC-kriterier
12. august 2011
Først opslået (Skøn)
15. august 2011
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
11. januar 2019
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
9. januar 2019
Sidst verificeret
1. januar 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Leukæmi, B-celle
- Leukæmi
- Leukæmi, lymfatisk, kronisk, B-celle
- Leukæmi, lymfoid
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Antirheumatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Cyclofosfamid
Andre undersøgelses-id-numre
- 11-048
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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