Combination of nivolumab and ipilimumab with 5-azacitidine in patients with myelodysplastic syndromes (MDS)
The goal of this clinical research study is to learn if nivolumab and/or ipilumumab, with or without azacitidine, are safe to give to patients with MDS. Researchers also want to learn if the study drug combinations can help to control the disease.
Disease Group: Leukemia,Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: Azacitidine,Ipilimumab,Nivolumab
Treatment Location: Only at MDACC
Sponsor: Bristol Myer Squibb,This study will be monitored by the MD Anderson IND Office and a protocol-specific monitoring plan will be followed.,nivolumab and ipilimumab
Primary: To determine the safety of nivolumab and ipilimumab, as single agents or in combination and with 5-azacitidine, in patients with MDS. Secondary: 1. To explore the clinical activity of nivolumab and ipilimumab, as single agents or in combination and with 5-azacitidine, in patients with MDS 2. To explore the biological activity of these compounds in patients with MDS.
IRB Review and Approval Date: 09/08/2015
Recruitment Status: Open
Projected Accrual: N/A
1) Patients with MDS (up to 20% blasts) of any risk as defined as: a.
Previously untreated; b. Previously treated with HMA agent. Patients
need to have relapsed or progressed after any number of cycles of HMA
therapy. Patients that do not respond to HMA therapy will also be
allowed in the study. Relapse or progression will be measured by IWG
2006 criteria. No response will be lack of clinical benefit after at
least 6 cycles of HMA therapy.
2) Age 18 years or older.
3) Adequate organ function: creatinine </=2.0 x ULN; serum bilirubin </=2.0 x ULN; AST and ALT </=2.0 x ULN.
4) ECOG performance status </=2
5) Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception 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 drugs. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
6) Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and a period of 31 weeks after the last dose of investigational drug.
7) Patients or their legally authorized representative must provide written informed consent.
1) History of another primary invasive malignancy that has not been
definitively treated or in remission for at least 2 years. Patients with
non-melanoma skin cancers or with carcinomas in situ are eligible
regardless of the time from diagnosis (including concomitant diagnoses).
2) Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs.
3) Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure NYHA Class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study.
4) Patients unwilling or unable to comply with the protocol.
5) History of pneumonitis.
6) Patients who are on high dose steroid (equivalent of prednisone more than 10 mg a day) or immune suppression medications.
7) Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]).
8) Patients with a history of Inflammatory Bowel Disease such as Crohn’s disease and ulcerative colitis.
9) Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months). Patients with history of HIV disease are also excluded from the study.
10) Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents.
11) Females who are pregnant or lactating.
12) For hypomethylating failure cohorts, treatment for MDS with any other drug not being an HMA with the following exceptions: Prior treatment with growth factors and/or lenalidomide is allowed for any cohort.
13) For hypomethylating failure cohorts only, more than 4 months since last cycle of HMA.
14) Prior treatment with allogeneic stem cell transplantation.
Information and next steps
Leukemia,Malignant neoplasms stated as primary lymphoid haematopoietic
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