- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT01183949
Effect of AT7519M Alone and AT7519M Plus Bortezomib in Patients With Previously Treated Multiple Myeloma
A Phase I/II Open-label Multicenter Study of AT7519M Alone and in Combination With Bortezomib in Patients With Previously Treated Multiple Myeloma
Przegląd badań
Szczegółowy opis
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 2
- Faza 1
Kontakty i lokalizacje
Lokalizacje studiów
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Massachusetts
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Boston, Massachusetts, Stany Zjednoczone, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Stany Zjednoczone, MA02115
- Massachusetts General Hospital
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Boston, Massachusetts, Stany Zjednoczone
- Dana Faber Cancer Institute
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New York
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New York, New York, Stany Zjednoczone, 10065
- Memorial Sloan-Kettering Cancer Centre
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Wisconsin
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Milwaukee, Wisconsin, Stany Zjednoczone, 53226
- MCW and Froedtert Clinical Cancer Center, Division of Neoplastic Diseases & Related Disorders
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
Inclusion Criteria:
- Ability to understand the risks of the study and provide signed informed consent
- Age 18 years or older
- Relapsed and or Refractory MM
- Disease progression following at least two systemic treatments for MM
- Patient must be refractory to the last bortezomib
- ECOG performance status 0, 1 or 2
Exclusion Criteria:
- Pregnant or lactating females. Patients of childbearing potential must use appropriate birth control throughout the study
- Inadequate liver function
- Renal impairment
- Neutrophil count <1.0 x 10^9 /litre in the absence of growth factors
- Platelet count <50 x 10^9 /litre in patients in whom <50% of bone marrow nucleated cells are plasma cells and <30 x 10^9 /litre in patients in whom ≥50 % of bone marrow nucleated cells are plasma cells
- Hemoglobin <8g/dl in the absence of transfusion
- Treated corrected calcium >ULN
- Serum creatine phosphokinase >ULN
- All previous cytotoxic therapies for MM must have been completed at least four weeks prior to treatment with AT7519M (two weeks for all non-cytotoxic therapy)
- Patients may be receiving concomitant therapy with biphosphonates and low dose corticosteroids. Bisphosphonates doses should be stable for at least 30 days prior to study drug administration. Corticosteroids doses should be stable for at least 7 days prior to study treatment
- Prior peripheral stem cell transplant within 12 weeks
- Evidence of mucosal or internal bleeding and/or platelet transfusion refractory (unable to maintain a platelet count >50 x 10^9 /litre)
- Ongoing infection requiring treatment
- Previous radiotherapy within 2 weeks of the start of the study
- Having previously received treatment with a cyclin-dependent kinase or GSK3beta inhibitor
- Incomplete recovery from previous radiotherapy other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity
- Prior radiotherapy to the head and neck region for head and neck tumors
- Previous malignancy, except for non-melanomatous skin carcinomas, in situ carcinomas or malignancies with low risk of recurrence.
- Any severe or uncontrolled systemic conditions (e.g. systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
- Incomplete recovery from surgery other than stable < Grade 2 toxicity
- Peripheral neuropathy > Grade 2
- Abnormal left ventricular ejection fraction (< lower limit of normal for the institution for a patient of that age) on echocardiogram
- History of an ischemic cardiac event, including myocardial infarction within 3 months of study entry
- Congestive cardiac failure of ≥ grade 3 severity according to NYHA functional classification
- Unstable cardiac disease
- History or presence of bradycardia (≤60bpm), left bundle branch block, heart block, cardiac pacemaker or significant atrial tachyarrhythmias
- If the patient will receive bortezomib (Velcade) during part C of the study, concurrent treatment with any medication known strongly to inhibit or induce CYP3A4, CYP1A2 and CYP2C19 which cannot be discontinued at least two week prior to treatment with AT7519M (other than corticosteroids)
- Concurrent treatment with any medication that prolongs QT interval and may induce Torsades de Pointes and which cannot be discontinued at least two weeks prior to treatment with AT7519M
- Family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy
- Previous history of drug-induced QTc prolongation
- Screening 12-lead ECG with measurable QTc interval according to Fridericia's Correction of >450 msecs
- Screening 12-lead ECG with ST depression >1 mm in 2 or more leads or T wave inversion in 2 or more contiguous leads
- Prior history of infection with human immunodeficiency virus (HIV), known active hepatitis B or C viruses
- Diffuse infiltrative pulmonary or pericardial disease
- Known hypersensitivity to bortezomib, boron or any of the excipients of VelcadeTM
- Epilepsy or other convulsive disorder requiring active management
- Serious psychiatric illness, active alcoholism or drug addiction that may hinder or confuse follow up evaluation
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: Treatment
Patients will be enrolled into 3 groups which will run sequentially.
Groups A and B will receive AT7519M only, whereas Group C will receive AT7519M in combination with Bortezomib.
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Part A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities. Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy. Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose.
Part C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design.
The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2.
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib
Ramy czasowe: Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)
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Efficacy will be assessed using the International Multiple Myeloma Working Group (IMWG) Response Criteria
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Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Assess the type, incidence and severity of clinically significant treatment emergent adverse events as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V 4.03
Ramy czasowe: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
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Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
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To define the pharmacokinetic profile of AT7519M and bortezomib when administered alone or in combination with bortezomib
Ramy czasowe: 2 cycles (i.e an average of 42 days)
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The pharmacokinetic evaluation will include the calculation of plasma clearance and elimination phase half-life for AT7519M and bortezomib
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2 cycles (i.e an average of 42 days)
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To identify the maximum tolerated dose (MTD) of AT7519M in combination with bortezomib
Ramy czasowe: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
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The MTD will be based on the incidence of dose limiting toxicities
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Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
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Współpracownicy i badacze
Sponsor
Współpracownicy
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
- Choroby układu odpornościowego
- Nowotwory
- Choroby hematologiczne
- Bortezomib
- Środki przeciwnowotworowe
- Zaburzenia limfoproliferacyjne
- Zaburzenia immunoproliferacyjne
- Nowotwory według typu histologicznego
- Nowotwory, komórki plazmatyczne
- Zaburzenia hemostatyczne
- Paraproteinemie
- Zaburzenia białek krwi
- Zaburzenia krwotoczne
Dodatkowe istotne warunki MeSH
- Choroby układu krążenia
- Choroby naczyniowe
- Choroby układu odpornościowego
- Nowotwory według typu histologicznego
- Nowotwory
- Zaburzenia limfoproliferacyjne
- Zaburzenia immunoproliferacyjne
- Choroby hematologiczne
- Zaburzenia krwotoczne
- Zaburzenia hemostatyczne
- Paraproteinemie
- Zaburzenia białek krwi
- Szpiczak mnogi
- Nowotwory, komórki plazmatyczne
- Środki przeciwnowotworowe
- Bortezomib
Inne numery identyfikacyjne badania
- AT7519M/0004
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Badania kliniczne na AT7519M
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NCIC Clinical Trials GroupAstex Pharmaceuticals, Inc.ZakończonyChłoniak z komórek płaszczaKanada
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NCIC Clinical Trials GroupAstex Pharmaceuticals, Inc.ZakończonyPrzewlekła białaczka limfocytowaKanada
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National Cancer Institute (NCI)Aktywny, nie rekrutującyZaawansowany złośliwy nowotwór lity | Przerzutowy złośliwy nowotwór lity | Nieoperacyjny lity nowotwórStany Zjednoczone