- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01120834
Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory Diffuse Large b Cell Lymphoma (DLBCL)
Phase I/II Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory DLBCL
Panoramica dello studio
Descrizione dettagliata
Eligible subjects will have biopsy proven relapsed or refractory DLBCL, have preserved hematologic and other organ function, and have either progressed following or be inappropriate candidates for autologous stem cell transplantation.
Patients will be treated with 5-azacitidine via subcutaneous administration and vorinostat orally at four different dose levels as described below:
- Dose level 1: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on Days 1-7.
- Dose level 2: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-7.
- Dose level 3: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on Days 1-14.
- Dose level 4: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-14.
Each cycle will be of 28 days and patients will be treated for up to 6 cycles.
Up to 8 patients will be enrolled at each dose level. If at any time 2 patients in a given cohort experience DLT, enrollment to that level will be discontinued.
Efficacy will be assessed by standard radiographic and other criteria at baseline and at the end of treatment to determine ORR. Patients will be followed for 2 years or until disease progression.
Tumor samples will be obtained for correlative studies at baseline through core needle or surgical biopsy, with an additional biopsy performed on day 15 of cycle 1 as a pharmacodynamic endpoint.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
New York
-
New York, New York, Stati Uniti, 10065
- Weill Cornell Medical College
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Patients must have histologically confirmed diffuse large B cell lymphoma, relapsed after or resistant to prior systemic therapy.
- Subjects must have measurable disease on cross sectional imaging that is at least 1.5 cm in diameter.
- Patients should have relapsed following or be deemed ineligible for autologous stem cell transplantation. There is no limit to number of prior therapies.
- Age > = 18 years.
- ECOG performance status < = 2.
Patients must have normal organ and marrow function as defined below:
- ANC > = 1,000/uL
- platelets > = 75,000//uL
- total bilirubin < = 2 X upper limit of normal
- AST(SGOT)/ALT(SGPT) < = 2.5 X upper limit of normal
- Serum creatinine < = 1.5 X upper limit of normal (ULN)
- Women of childbearing potential must have a negative serum pregnancy test prior to treatment
- The effects of these investigational agents on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A woman who becomes pregnant while participating in the study must withdraw from the study immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Prior allogeneic transplant
- Patients may not be receiving any other investigational agents.
- Patients may not have previously received anti-lymphoma therapy with an HDAC inhibitor (.e.g. Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid). Patients who have received an HDAC inhibitor for another indication such as epilepsy may enroll after a 30-day washout period
- Patients with known active CNS lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible..
- Patients with known hypersensitivity to azacytidine, vorinostat or mannitol.
- Patients with a currently active second malignancy.
- Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- QTc interval > 0.470. Consider discontinuation of medications that prolong QTc interval to eliminate this exclusion if medically appropriate.
- Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: all subjects
|
Each cycle = 28 days. Subjects may receive up to 6 cycles.
Each cycle = 28 days. Subjects receive up to 6 cycles. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Overall Response Rate (ORR)
Lasso di tempo: 2 cycles
|
Overall Response Rate (ORR)
|
2 cycles
|
Collaboratori e investigatori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
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
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Inibitori dell'istone deacetilasi
- Azacitidina
- Vorinostat
Altri numeri di identificazione dello studio
- 0912010795
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 .