- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT04961801
Acalabrutinib for GVHD Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia
GVHD remains a major cause of morbidity and mortality following SCT. The current standard of care for prophylaxis against GVHD includes tacrolimus and methotrexate.
This study proposes to utilize acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, for GVHD prophylaxis following allogeneic SCT.
The hypothesis is that the addition of acalabrutinib to our institutional standard GVHD prophylaxis (tacrolimus and methotrexate) is safe, feasible, and effective in reducing both the incidence and severity of acute GVHD.
Panoramica dello studio
Stato
Intervento / Trattamento
Tipo di studio
Fase
- Fase 2
- Fase 1
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Willingness and ability to sign the study-specific informed consent form
- Willingness to comply with all study procedures and attend all study visits.
- Participant with (a) B-cell malignancies or (b) AML (CD117 positive) who are undergoing allogeneic SCT at Penn State Cancer Institute from an 8/8 matched unrelated donor. Donor selection and screening criteria are to comply with 21 CRF Part 1271.
- Male or female participant, age ≥ 18 and ≤ 75 years.
- Ability to swallow oral medication.
- Women of childbearing potential (WOCP) as defined as not surgically sterile or not postmenopausal must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 7 days of beginning the condition regimen.
- Men and WOCP must agree to use 2 medically accepted method of contraception and must agree to continue use this method while on the trial and through at least one week after the last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) withdrawal, spermicides only, or lactational amenorrhea are not acceptable methods of contraception. WOCP must use a medically accepted method of contraception and must agree to continue use this method from the time of signing the informed consent through at least one week after the last dose of study drug.
- Karnofsky Performance Scale (KPS) equal to or greater than 70%.
Exclusion Criteria:
- Renal dysfunction with eGFR <30/mL/minute/1.73 m2 by Cockroft-Gault formula.
- Participant requires warfarin or vitamin K antagonist within one week of acalabrutinib administration.
- Participant requires treatment with a strong cytochrome P450 3A inducer or inhibitor.
- Treatment with post-transplant cyclophosphamide
- Treatment with any other investigational products within 21 days of conditioning regimen.
- Known hypersensitivity to acalabrutinib, tacrolimus and methotrexate and their excipients.
- Active uncontrolled infections
- Human immunodeficiency virus (HIV) positivity.
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
- Diagnosed or treated for another malignancy within 2 years before study registration or previously diagnosed with another malignancy and have any evidence of residual disease. Participant with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
- Participant with coagulopathy or bleeding disorder.
- Known hepatic cirrhosis or severe pre-existing hepatic impairment (ALT and/or AST more than 3x greater than upper limit of normal, Total Bilirubin more than 2x greater than upper limit of normal)
- Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
- Uncontrolled or symptomatic cardiac arrhythmia
- Left ventricular ejection fraction (LVEF) < 40% as assessed by echocardiogram or radionuclide angiography, or NYHA class 3 or 4 heart failure
- Myocardial infarction within 6 months of signing consent.
- History of stroke or intracranial hemorrhage within 6 months of signing consent.
- Breastfeeding or pregnant.
- Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication.
- Suspected or confirmed PML(Progressive Multifocal Leukoencephalopathy)
- Requires treatment with proton-pump inhibitors. (Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment.)
- FVC, FEV1, or DLCO (corrected with hemoglobin) less than 40% of expected value.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
- Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- Concurrent participation in another therapeutic clinical trial.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Acalabrutinib in combination with tacrolimus and methotrexate
|
For Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Dose-limiting toxicity
Lasso di tempo: 30 days
|
Dose-limiting toxicity of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
|
30 days
|
Maximum tolerated dose (MTD)
Lasso di tempo: 30 days
|
Maximum tolerated dose (MTD) of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
|
30 days
|
acute GVHD grade II-IV
Lasso di tempo: 180 days
|
Incidence of acute GVHD grade II-IV by day 180 for Phase II part of the study
|
180 days
|
Collaboratori e investigatori
Sponsor
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Anticipato)
Completamento primario (Anticipato)
Completamento dello studio (Anticipato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Linfoma
- Leucemia
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti dermatologici
- Agenti di controllo riproduttivo
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Inibitori della calcineurina
- Metotrexato
- Tacrolimo
- Acalabrutinib
Altri numeri di identificazione dello studio
- PSCI-18-128
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Acalabrutinib, tacrolimus, methotrexate
-
Acerta Pharma BVAstraZenecaAttivo, non reclutanteLinfoma mantellare (MCL)Stati Uniti, Polonia, Italia
-
AstraZenecaParexelCompletatoCOVID-19 | Linfoma a cellule del mantelloGermania
-
AstraZenecaAcerta Pharma, LLCCompletatoFarmacocinetica | BiodisponibilitàStati Uniti
-
Acerta Pharma BVNational Institutes of Health (NIH)Attivo, non reclutanteLeucemia linfatica cronica | Piccolo linfoma linfociticoStati Uniti
-
Acerta Pharma BVAstraZenecaCompletatoInsufficienza epatica | Soggetti sani | Insufficienza epaticaStati Uniti
-
Novartis PharmaceuticalsCompletatoDestinatario del trapianto di fegatoBelgio, Spagna, Germania, Italia, Australia, Stati Uniti, Olanda, Irlanda, Svezia, Brasile, Colombia, Francia, Federazione Russa, Argentina, Cechia, Regno Unito
-
AstraZenecaCompletatoBioequivalenzaStati Uniti
-
Novartis PharmaceuticalsCompletatoTrapianto di fegatoStati Uniti, Belgio, Colombia, Spagna, Germania, Italia, Australia, Israele, Francia, Ungheria, Olanda, Argentina, Canada, Irlanda, Svezia, Brasile, Regno Unito, Federazione Russa, Repubblica Ceca
-
Acerta Pharma BVAttivo, non reclutanteMacroglobulinemia di Waldenström (WM)Spagna, Stati Uniti, Regno Unito, Francia, Italia, Grecia, Olanda
-
Acerta Pharma BVAttivo, non reclutanteLinfoma mantellare (MCL)Belgio, Francia, Regno Unito, Stati Uniti, Italia, Polonia, Olanda, Australia, Cechia, Spagna