- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00101088
Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia
A Phase I Study of CCI-779 in Combination With Imatinib Mesylate in Chronic Myelogenous Leukemia
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
OBJECTIVES:
I. Determine the safety and tolerability of temsirolimus when administered with imatinib mesylate in patients with chronic myelogenous leukemia.
II. Determine potential dose-limiting toxic effects of this regimen in these patients.
III. Determine, preliminarily, hematologic and cytogenetic response rates in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of temsirolimus.
Patients receive temsirolimus intravenously (IV) over 30 minutes once on days 1, 8, 15, and 22 and oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients receive 2 additional courses beyond maximal response. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for survival.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
California
-
Orange, California, Forente stater, 92868
- University of California Medical Center At Irvine-Orange Campus
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
Histologically confirmed chronic myelogenous leukemia (CML)
Philadelphia chromosome-positive OR Bcr-Abl-positive disease, meeting 1 of the following criteria:
Accelerated phase, defined by at least 1 of the following:
- 10-19% blasts in the peripheral blood or bone marrow
- At least 20% basophils in peripheral blood or bone marrow
- Platelet count < 100,000/mm^3 (unrelated to therapy)
- Platelet count > 1,000,000/mm^3 (unresponsive to therapy)
- Increasing splenomegaly AND increasing WBC count (unresponsive to therapy)
- Clonal evolution
Blast phase, defined by 1 of the following:
- At least 20% blasts in peripheral blood or bone marrow
- Extramedullary disease
Chronic phase, defined by all of the following:
- Less than 10% blasts in peripheral blood or bone marrow
- Less than 20% basophils in peripheral blood or bone marrow
- Platelet count > 100,000/mm^3
- Absence of clonal evolution
May have received and/or failed prior imatinib mesylate therapy
Patients not previously treated with imatinib mesylate receive oral imatinib mesylate once daily 14 days before beginning study drug
- Must be able to tolerate 600 mg per day of imatinib mesylate before starting CCI-779
Patients with chronic phase disease must have failed prior imatinib mesylate at a dose ≥ 600 mg/day, as defined by 1 of the following:
- Must not have achieved or must have lost hematologic response within 3 months after the start of imatinib mesylate
- Must not have achieved or must have lost cytogenetic response after 6 months of treatment with imatinib mesylate
- Must not have achieved or must have lost major cytogenetic response after 12 months of treatment with imatinib mesylate
- Must have lost complete cytogenetic response
- Bone marrow aspirate and biopsy with cytogenetics and fluorescent in situ hybridization confirming t(9;22) completed within the past 28 days
- Performance status - SWOG 0-2
- More than 3 months
- See Disease Characteristics
- Bilirubin normal
- AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if suspected liver involvement with leukemia)
- Creatinine normal
- Creatinine clearance > 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Ejection fraction ≥ 50% by echocardiogram or MUGA scan for patients with known positive cardiac history (e.g., heart failure, coronary artery disease, cardiomegaly on prior chest x-ray, or valvular heart disease)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Fasting cholesterol ≤ 350 mg/dL
- Fasting triglycerides ≤ 400 mg/dL
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to temsirolimus or imatinib mesylate
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
- No other active malignancy except nonmelanoma skin cancer
- No other uncontrolled illness
- At least 48 hours since prior interferon alfa for CML
- At least 6 weeks since prior stem cell transplantation
- No concurrent biologic agents
- No concurrent prophylactic colony-stimulating factors
- At least 24 hours since prior hydroxyurea for CML
- At least 7 days since prior mercaptopurine or vinca alkaloids for CML
- At least 7 days since prior low-dose cytarabine (< 30 mg/m^2 every 12-24 hours) for CML
- At least 14 days since prior homoharringtonine for CML
- At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5-7 days) for CML
- At least 21 days since prior anthracyclines, mitoxantrone, cyclophosphamide, etoposide, or methotrexate for CML
- At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12-24 hours for 6-12 doses) for CML
- At least 6 weeks since prior busulfan for CML
- No concurrent hydroxyurea
- No other concurrent chemotherapy
- At least 7 days since prior steroids for CML
- No prior organ transplantation
- More than 2 weeks since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)
- Recovered from all prior therapy
- Prior experimental therapy allowed provided completion of treatment corresponds to a duration > 5 half-lives of the experimental drug or any known active metabolite before study
- No concurrent cyclosporine
- No concurrent anagrelide
- No concurrent oral anticoagulants, including warfarin
- No concurrent CYP3A4 inducers or inhibitors
- No concurrent tacrolimus
- No concurrent plasmapheresis
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer therapies
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Treatment (imatinib mesylate, temsirolimus)
Patients receive temsirolimus IV over 30 minutes once on days 1, 8, 15, and 22 and oral imatinib mesylate once daily on days 1-28.
Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression
|
Korrelative studier
Gis muntlig
Andre navn:
Gitt IV
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
Unacceptable toxicity graded according to the NCI CTCAE version 3.0
Tidsramme: Up to 5 years
|
Up to 5 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Sykdomsprogresjon
Tidsramme: Inntil 5 år
|
Inntil 5 år
|
|
Overlevelse
Tidsramme: Inntil 5 år
|
Inntil 5 år
|
|
Duration of response
Tidsramme: Up to 5 years
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Presented using descriptive statistics.
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Up to 5 years
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Tiong Ong, University of California Medical Center At Irvine-Orange Campus
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Neoplasmer etter histologisk type
- Neoplasmer
- Benmargssykdommer
- Hematologiske sykdommer
- Myeloproliferative lidelser
- Neoplastiske prosesser
- Celletransformasjon, neoplastisk
- Karsinogenese
- Leukemi
- Leukemi, myeloid
- Leukemi, myelogen, kronisk, BCR-ABL positiv
- Leukemi, Myeloid, Kronisk fase
- Blast krise
- Leukemi, Myeloid, Akselerert fase
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Enzymhemmere
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antibakterielle midler
- Proteinkinasehemmere
- Antibiotika, antineoplastisk
- Antifungale midler
- Imatinibmesylat
- Sirolimus
Andre studie-ID-numre
- NCI-2009-00073
- UCI-04-04
- R21CA112936 (U.S. NIH-stipend/kontrakt)
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