- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01132586
Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia
Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia
Studieöversikt
Status
Betingelser
- Akut myeloid leukemi som härrör från tidigare myelodysplastiskt syndrom
- Tidigare behandlat myelodysplastiskt syndrom
- Återkommande akut myeloid leukemi hos vuxna
- Sekundär akut myeloid leukemi
- Obehandlad akut myeloid leukemi hos vuxna
- Sekundärt myelodysplastiskt syndrom
- de Novo myelodysplastiskt syndrom
- Akut myeloid leukemi hos vuxna med Inv(16)(p13.1q22); CBFB-MYH11
- Vuxen akut myeloid leukemi med t(16;16)(p13.1;q22); CBFB-MYH11
- Akut myeloid leukemi relaterad till alkyleringsmedel
- Vuxen akut myeloid leukemi med t(9;11)(p22;q23); MLLT3-MLL
- Vuxen akut promyelocytisk leukemi med t(15;17)(q22;q12); PML-RARA
- Vuxen akut myeloid leukemi med t(8;21)(q22;q22); RUNX1-RUNX1T1
Detaljerad beskrivning
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with conventional chemotherapy in two separate cohorts of patients with 1) relapsed or refractory acute myeloid leukemia (AML) and 2) age >= 60 with untreated AML and recommend starting doses for phase II studies of this combination of agents.
SECONDARY OBJECTIVES:
I. To define the qualitative and quantitative toxicities of these combinations of agents in regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of these combinations of agents in patients with poor risk AML.
III. To conduct pharmacodynamic studies to investigate the potential mechanism of lenalidomide activity in this trial.
OUTLINE: This is a dose-escalation study of lenalidomide.
INDUCTION:
COHORT I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, cytarabine intravenously (IV) continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.
COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.
Patients with residual disease on day 18 undergo a second course of induction therapy.
CONSOLIDATION:
COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
-
-
Ohio
-
Columbus, Ohio, Förenta staterna, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
Cohort 1: Patients must be age >= 18 and < 65 with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS); high risk MDS is defined as international prognosis scoring system (IPSS) score of 1.5 or higher; eligible patients will have a score of 1.5 or higher at any time from diagnosis to screening
- Cohort 2: Patients must be age >= 18 with previously untreated AML; favorable risk AML patients < 60 years of age are excluded; these are defined as core binding factor (CBF) AML patients and characterized by cytogenetic or molecular evidence of CBF leukemia; untreated AML patients < 60 years of age must be negative on screening for CBF leukemia by cytogenetic or molecular analysis (Note: Prior therapy for MDS is permitted)
- Patients with secondary AML or therapy-related disease (transformed [t]-AML/MDS) are eligible
- If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin < 2.0 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper limit of normal
- Creatinine < 2.0 mg/dL AND creatinine clearance (calculated) >= 50 mL/min
- Left ventricular ejection fraction (LVEF) >= 40%
- Patients who have previously received lenalidomide, idarubicin, and/or cytarabine are eligible provided that the combination of the 3 agents has never before been administered, and that no lenalidomide has been administered for at least 6 months
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a minimum sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; these methods of birth control must be used for the duration of study participation and for 28 days after lenalidomide discontinuation; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- Ability to understand and willingness to sign the written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have taken lenalidomide within the last 6 months
- Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
- Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
- Patients with history of medically serious allergic reactions or non-hematologic toxicities attributed to the agents in this trial such as lenalidomide or thalidomide or compounds of similar chemical or biologic composition that are not easily managed, or patients with a history of cerebellar toxicity to cytarabine
- Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled
- Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Pregnant women or women who are breastfeeding; additional pregnancy testing before, during, and after lenalidomide treatment is required, as well as requirements for contraception before, during, and after lenalidomide treatment
- Patients with advanced malignant solid tumors are excluded; patients with active additional hematologic malignancies are excluded
- Patients with a history of neurologic toxicity with cytarabine are excluded
- As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control
- Known human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in HIV + patients once safety of the combination has been demonstrated
Studieplan
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: Treatment (lenalidomide, cytarabine, idarubicin)
INDUCTION: COHORT I: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7. COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above. Patients with residual disease on day 18 undergo a second course of induction therapy. CONSOLIDATION: COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity. COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. |
Korrelativa studier
Korrelativa studier
Andra namn:
Givet IV
Andra namn:
Givet PO
Andra namn:
Givet IV
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
MTD of lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Tidsram: 28 days
|
28 days
|
Sekundära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
Qualitative and quantitative toxicities, graded using NCI CTCAE version 4.0
Tidsram: Up to 30 days post-treatment
|
Up to 30 days post-treatment
|
|
Therapeutic response, assessed using International Working Group criteria
Tidsram: Up to 30 days post-treatment
|
Up to 30 days post-treatment
|
|
Pharmacodynamic studies, including micro-ribonucleic acid (miRNA)-181 family and target gene expression, CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) expression, and genes involved in erythroid differentiation
Tidsram: Baseline, day 5, and day 28
|
Baseline, day 5, and day 28
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: William Blum, Ohio State University Comprehensive Cancer Center
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Neoplasmer efter histologisk typ
- Neoplasmer
- Sjukdom
- Benmärgssjukdomar
- Hematologiska sjukdomar
- Neoplastiska processer
- Precancerösa tillstånd
- Syndrom
- Myelodysplastiska syndrom
- Leukemi
- Leukemi, myeloid
- Leukemi, Myeloid, Akut
- Neoplasma Metastas
- Preleukemi
- Leukemi, Promyelocytisk, Akut
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Anti-infektionsmedel
- Antivirala medel
- Enzyminhibitorer
- Antimetaboliter, antineoplastiska
- Antimetaboliter
- Antineoplastiska medel
- Immunsuppressiva medel
- Immunologiska faktorer
- Topoisomeras II-hämmare
- Topoisomerasinhibitorer
- Angiogeneshämmare
- Angiogenesmodulerande medel
- Tillväxtämnen
- Tillväxthämmare
- Antibiotika, antineoplastiska
- Lenalidomid
- Cytarabin
- Idarubicin
Andra studie-ID-nummer
- NCI-2011-01375 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (U.S.S. NIH-anslag/kontrakt)
- UM1CA186712 (U.S.S. NIH-anslag/kontrakt)
- 8455 (Annan identifierare: CTEP)
- U01CA076576 (U.S.S. NIH-anslag/kontrakt)
- OSU-10016
- CDR0000673883
- OSU 10016 (Annan identifierare: Ohio State University Comprehensive Cancer Center)
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