- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00724984
Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma (PCYC-0403)
Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
California
-
San Francisco, California, Forenede Stater, 94143
- University of California, San Francisco
-
-
Illinois
-
Chicago, Illinois, Forenede Stater, 60611
- Northwestern University Medical School
-
-
Indiana
-
Lafayette, Indiana, Forenede Stater, 47905
- Horizon Oncology Center
-
-
Massachusetts
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Worcester, Massachusetts, Forenede Stater, 01655
- University of Massachusetts Medical School
-
-
Missouri
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St. Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
-
-
Nebraska
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Omaha, Nebraska, Forenede Stater, 68114
- Nebraska Methodist Hospital
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Omaha, Nebraska, Forenede Stater, 68198
- University of Nebraska Medical Center
-
-
Vermont
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Burlington, Vermont, Forenede Stater, 05405
- University of Vermont and Fletcher Allen Health Care
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
• age ≥ 18 years
- Phase I: Any measurable, histologically confirmed, and previously treated lymphoma
Phase II: Measurable, histologically confirmed, and previously treated lymphoma in one of the following categories:
- Follicular non-Hodgkin's Lymphoma
- Mantle cell lymphoma
- Ability to swallow oral capsules without difficulty
- Estimated life expectancy > 12 weeks
- ECOG performance status ≤ 1
- Willing and able to sign a written informed consent
Exclusion Criteria:
• More than four prior systemic treatment regimens (not counting maintenance rituximab; salvage therapy/conditioning regimen preceding autologous bone marrow transplantation [ABMT] and ABMT count as one regimen)
- Allogeneic bone marrow transplant
- Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing
- Major surgery within 4 weeks before first day of study drug dosing
- CNS lymphoma or a history of meningeal carcinomatosis
- Prior treatment with an HDAC inhibitor (unless for treatment of Mycosis fungoides or Sézary syndrome)
- Creatinine > 1.5 x institutional upper limit of normal (ULN) or creatinine clearance ≤ 50 mL/min
- Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
- AST and ALT > 2.5 x institutional ULN
- Platelet count < 75,000/µL for Phase I and <100,000>µL for Phase II
- Absolute neutrophil count (ANC) < 1500/µL
- Malabsorption
- Corticosteroids > 20 mg prednisone equivalent per day (topical, inhaled, or nasal corticosteroids are permitted)
- Concurrent therapeutic anticoagulation (Phase I only)
- Uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements
- Risk factors for, or use of drugs known to prolong QTc interval or that may be associated
- QTc prolongation (defined as a QTc ≥ 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc ≥ 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
- For patients with history of myocardial infarction, congestive heart failure, abnormal left ventricular ejection fraction (LVEF), and/or prior anthracycline exposure, LVEF < 50%, as assessed by ventriculography (nuclear or heart catheterization) or echocardiogram, when performed within 28 days of first dose of study drug.
- For patients with history of coronary artery disease, a cardiac stress test (either exercise or pharmacologic) that demonstrates clinically significant abnormalities when performed within 28 days of first dose of study drug.
- Known HIV infection.
- Other medical or psychiatric illness or organ dysfunction which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent.
- Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound).
- Women of child-bearing potential, or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: 1
|
Phase I Dose Escalation: Up to 5 cohorts will receive PCI-24781 orally at doses starting at 30mg/m2 two times a day approximately 4-6 hours apart ("BID"), up to 90mg/m2 administered 5 days/week during the first 21 days of each 28 day cycle until the maximum tolerated dose (MTD) is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive PCI-24781 BID for 7 days every other week (2 times in a 28 day cycle). Phase II Efficacy Evaluation: All patients will receive PCI-24781 orally at the dosage and regimen determined in Phase I. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Phase I (Dose Escalation Phase): MTD and DLTs of PCI-24781 Administered Twice Daily (BID) Measure: Disease Response
Tidsramme: From the Date of PCI-24781 first administration to Cycle 2 Day 1
|
Number of patients experienced DLT in each cohort
|
From the Date of PCI-24781 first administration to Cycle 2 Day 1
|
Phase II: Overall Response Rate (CR+PR)
Tidsramme: From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles
|
From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Thorsten Graef, MD, Pharmacyclics LLC.
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- PCYC-0403
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-
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