- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00820508
Safety and Tolerability of CHR-2845 to Treat Haematological Diseases or Lymphoid Malignancies (CHR-2845-001)
25 november 2011 uppdaterad av: Chroma Therapeutics
A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-2845, in Patients With Advanced or Treatment Refractory Haematological Diseases or Lymphoid Malignancies
The purpose of this study is to determine whether the histone deacetylase inhibitor CHR-2845 is tolerated in patients with haematological diseases and lymphoid malignancies.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
CHR-2845 is a novel type of histone deacetylase inhibitor (HDACi) for use in cancer that, in addition to having broad ranging anti-proliferative activity against transformed cells, is designed to have an increased therapeutic window against diseases which involve cells of the monocyte-macrophage lineage.
There are several HDACi's in clinical development and one, SAHA (Vorinostat, Zolinza®), has recently been approved for use in the treatment of cutaneous T-cell lymphoma.
CHR-2845 is a cell-permeant ester that is metabolised to give an active acid, CHR-2847, which selectively accumulates in monocytes and macrophages.
This results in a 20-100 fold increase in anti-proliferative potency of CHR-2845 for monocytic over non-monocytic tumour cells.
This selectivity should lead to an increased therapeutic window in haematological malignancies involving cells of the monocyte lineage (AML M4, AML M5 and CMML).
In addition, there is increasing evidence that monocytes and macrophages associated with some haematological tumours (tumour-associated macrophages (TAMs)) are involved in supporting the growth and spread of the tumour.
This clinical trial will focus on haematological and lymphoid malignancies with the intention of evaluating the safety and tolerability of CHR-2845.
Additionally it will compare response in patients where monocytes/macrophages are important disease drivers, with the response in other patients.
This will allow an early determination of the potential improvement in therapeutic window afforded by the monocyte/macrophage directed HDACi activity.
Studietyp
Interventionell
Inskrivning (Faktisk)
18
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Antwerp, Belgien, 2060
- ZNA Stuivenberg
-
-
-
-
-
Marseille, Frankrike
- Institut Paoli-Calmettes
-
-
-
-
-
Amsterdam, Nederländerna, 1007 MB
- VU University Medical Center
-
Rotterdam, Nederländerna, 3015 CE
- Erasmus University Medical Center
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Signed, informed consent
- Confirmed malignant haematological disease or lymphoid malignancy refractory to standard therapy or for which no standard therapy exists, including acute leukemias, MDS, CML, CLL, CMML, multiple myeloma and Non-Hodgkin's Lymphomas/Hodgkin's disease
- Patients shall have recovered from all acute adverse effects of prior therapies, with the exception of alopecia and grade 1 neuropathy where recovery is not required
Adequate bone marrow, hepatic and renal function including the following:
- Patients with high blast counts can be included if they can be controlled by the use of hydroxyurea (500 mg -3,000 mg daily).
- Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilbert's Syndrome
- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit
- Creatinine ≤ 1.5 x upper normal limit
- Age ≥ 18 years
- Performance status (PS) ≤ 2 - Eastern Cooperative Oncology Group (ECOG) scale
- Estimated life expectancy greater than 3 months
- Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment.
Exclusion Criteria:
- Patients receiving anti-cancer therapy or use of other investigational agents within 21 days prior to trial entry (or a longer period depending on the defined characteristics of the agents used. Bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial. Patients must have recovered from all transient toxicity induced by prior therapy
- Patients with co-existing active infection, graft versus host disease or serious concurrent illness
- Patients who have failed to recover from or after a bone marrow transplantation or haematopoietic stem cell transplantation
- The following diseases are excluded: Burkitt's lymphoma, primary effusion lymphoma, precursor B-cell lymphoblastic lymphoma, symptomatic central nervous system (CNS) lymphoma, CML blast crisis
Patients with significant cardiovascular disease as defined by:
- history of congestive heart failure requiring therapy
- history of angina pectoris requiring treatment or myocardial infarction within 6 months prior to trial entry
- presence of severe valvular heart disease
- presence of an atrial or ventricular arrhythmia requiring treatment
- Left Ventricular Ejection Fraction (LVEF) below the normal range at the study centre
- Uncontrolled hypertension
- A history of abnormal QTc intervals or an average QTc interval at screening ≥450 msec
- Any medical or other condition that in the investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Gastrointestinal disorders that may interfere with absorption of the study drug
- Patients with known brain tumours or metastases
- More than 6 prior chemotherapy regimens
- Patients requiring growth factor support (erythropoietin, Granulocyte/monocyte Colony Stimulating Factor (GM/CSF), etc)
- Patients requiring palliative radiotherapy within the last 4 weeks prior to study entry
- Uncontrolled hypercalcaemia (CTCAE v3 grade 2 or higher)
- Abnormal plasma potassium or magnesium levels (Common Terminology Criteria for Adverse Events (CTCAE) v3 grade 3 or greater) despite therapy
- Pregnant or breast-feeding women
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: 1
Oral, once daily administration of CHR-2845 to determine safety and tolerability
|
Once daily oral ingestion of capsules (10, 40 or 80mg), dose depending on cohort, treatment cycle of 28 days
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
---|---|
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD)
Tidsram: 28 days
|
28 days
|
Sekundära resultatmått
Resultatmått |
Tidsram |
---|---|
To determine pharmacokinetic parameters of CHR-2845 and the active metabolite CHR-2847
Tidsram: days 1 and 28
|
days 1 and 28
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Bob Löwenberg, M.D, Erasmus Medical Center
- Huvudutredare: Gert Ossenkoppele, M.D, Amsterdam UMC, location VUmc
- Huvudutredare: Pierre Zachee, MD, ZNA Stuivenberg
- Huvudutredare: Norbert Vey, MD, Institut Paoli-Calmettes
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 december 2008
Primärt slutförande (Faktisk)
1 juli 2011
Avslutad studie (Faktisk)
1 juli 2011
Studieregistreringsdatum
Först inskickad
9 januari 2009
Först inskickad som uppfyllde QC-kriterierna
9 januari 2009
Första postat (Uppskatta)
12 januari 2009
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
28 november 2011
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
25 november 2011
Senast verifierad
1 november 2011
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- CHR-2845-001
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Lymfoid malignitet
-
International Extranodal Lymphoma Study Group (IELSG)Aktiv, inte rekryterandeMucosa Associated Lymphoid Tissue (MALT) lymfomSpanien, Italien, Österrike
-
Grupo Español de Linfomas y Transplante Autólogo...Avslutad
Kliniska prövningar på CHR-2845
-
GlaxoSmithKlineAvslutadArtrit, reumatoidStorbritannien
-
University of California, IrvineUniversity of Maryland, Baltimore CountyHar inte rekryterat ännuSjälvmord | Psykos | Hälsovårdsutnyttjande | Familjemedlemmar
-
Rhode Island HospitalRekryteringPsykos nr/ÖvrigtFörenta staterna
-
Chroma TherapeuticsOkändAkut myeloid leukemiFörenta staterna
-
Chroma TherapeuticsAvslutadAkut myeloid leukemi | Multipelt myelom | Myelodysplastiskt syndromStorbritannien
-
Weill Medical College of Cornell UniversityCTI BioPharmaAvslutadMyelodysplastiskt syndromFörenta staterna
-
Icahn School of Medicine at Mount SinaiNational Institute of Mental Health (NIMH)RekryteringKlinisk högrisk för psykos (CHR)Förenta staterna
-
Chroma TherapeuticsQuintiles, Inc.AvslutadAkut myeloid leukemi | AMLFörenta staterna, Kanada, Nederländerna
-
Chroma TherapeuticsInstitute of Cancer Research, United KingdomAvslutadAvancerade solida tumörer
-
Chroma TherapeuticsAvslutadSäkerhetsstudie av histondeacetylasinhibitorn, CHR-3996, hos patienter med avancerade solida tumörerFast tumörNederländerna, Storbritannien