Phase I/II Study of Idarubicin, Cytarabine, and Nivolumab in patients with high-risk MDS and AML
The goal of this clinical research study is to find the highest tolerable dose of nivolumab that can be give in combination with idarubicin and cytarabine in patients with MDS and AML. The safety and effectiveness of this drug combination will also be studied.
Disease Group: Leukemia
Treatment Agent: Cytarabine,Idarubicin,Nivolumab
Treatment Location: Only at MD Anderson
Sponsor: Bistol Myers Squibb
1. For phase I portion of study: To determine the tolerability of the combination of idarubicin, cytarabine (ara-C), and nivolumab (IAN) in patients with high-risk MDS and AML. 2. For phase II portion of study: To determine event-free survival (EFS) where the events are defined as death or relapse using the combination of idarubicin, cytarabine, and nivolumab in patients with high-risk Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML).
IRB Review and Approval Date: 07/20/2015
Recruitment Status: Open
Projected Accrual: N/A
1) Diagnosis of 1) AML (WHO classification definition of >/= 20%
blasts), or 2) high risk MDS (defined as the presence of 10% blasts).
2) Patients aged 18 to 60 years are eligible. Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the PI.
3) In the Phase I portion, patients with relapsed or refractory AML/MDS are also eligible, as per the treating physician’s discretion.
4) For the Phase II portion of the study, patients must be chemo-naive, i.e. not have received any prior chemotherapy (except hydrea or one dose of ara-C </= 2g) for AML or MDS. They could have received hypomethylator agents, transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or hydrea or one dose of ara-C </= 2g in order to safely control hyperleucocytosis prior to enrollment.
5) Serum biochemical values with the following limits unless considered due to leukemia: ---Creatinine </= 1.5 mg/dl --- total bilirubin </= 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder --- transaminases (SG PT) </= 2.5 x ULN.
6) Ability to take oral medication.
7) Ability to understand and provide signed informed consent.
8) Baseline test of ejection fraction must be >/= 50%.
9) Performance status < 3, unless directly related to disease process as determined by the Principal Investigator.
1) Subjects with APL.
2) Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results.
3) Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study. --- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. --- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. --- Women must not be breastfeeding.
4) Continued:Men who are sexually active with WOCBP must use acceptable birth control methods. Acceptable birth control methods include: oral or injectable hormonal birth control, in trauterine devices(IUDS), and double barrier methods (for example a condom in combination with spermicide). Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
5) Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
6) History of cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within past 3 months.
7) Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
8) Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
9) Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
10) Active clinically serious and uncontrolled infection > CTCAE Grade 2 uncontrolled with antibiotics.
11) Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
12) Patients should be excluded if they are known to be positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
13) Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14) History of allergy to study drug components.
15) Prior immune checkpoint targeting drugs (e.g., anti PD1, and PDL1, anti-kir, anti CD137...etc)
Information and next steps
Phase I/Phase II
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