Safety and Clinical Activity Study of Combination Azacitidine and Avelumab in Patients With Acute Myeloid Leukemia (AML) and Minimal Residual Disease (MRD)

Withdrawn before enrolling · Phase 1/Phase 2

Conditions studied: Acute Myeloid Leukemia (AML), Minimal Residual Disease

In brief

This is a phase I / II study. The purposes of this study are to: 1) find out what effects, good and/or bad, the combination of the experimental drug avelumab and the drug azacitidine has on people with AML and MRD, and 2) test if the two drugs, avelumab and azacitidine, are effective in getting rid of AML MRD when the drugs are given together in combination.

Key facts

Study ID

NCT03699384

Run by

Memorial Sloan Kettering Cancer Center

People needed

0

Starts

2018-10-03

Expected to finish

2019-02-18

Last updated by the study team

2019-02-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must be ≥18 years of age.
• Subjects must have a history of AML as defined by WHO criteria. AML patients with any cytogenetic abnormalities are eligible except for patients with t (15;17) (acute promyelocytic leukemia). AML patients who have never undergone allogeneic stem cell transplant must have adverse-risk AML by ELN criteria77 to be eligible. Patients with a history of therapy related AML, myeloid sarcoma, or patients whose AML evolved from an antecedent MDS or MPN are also eligible. Patients with any molecular mutations are eligible.
• Subjects must have received therapy for AML and have a bone marrow biopsy within 28 days prior to registration that demonstrates a morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) as defined by European Leukemia Net (ELN) criteria. Patients with prior myeloid sarcoma must have no residual evidence of extramedullary leukemia.
• Subjects may have received any prior therapy for AML including cytotoxic agents, hypomethylating agents, or other therapeutics to achieve morphologic CR or CRi.
• Subjects must have MRD in a bone marrow aspirate within 28 days prior to registration from the same bone marrow sample which demonstrates morphologic CR. MRD is identified by multiparameter flow cytometry as a cell population showing deviation from normal antigen-expression patterns seen in specific cell lineages at specific stages of maturation. Any level of residual flow cytometric disease is considered MRD positive.
• Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
• Subjects or their legal representatives must be able to understand and sign an informed consent.
• Subjects must have ECOG PS of 0 to 2. 9. Subjects must have adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L, platelet count ≥ 50 × 10\^9/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
• Subjects must have adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN
• Subjects must have adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
• Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (Subjects with residual Grade 1-2 toxicity, for example Grade 1-2 peripheral neuropathy or residual alopecia, are allowed with approval of the principal investigator.)
• Negative serum pregnancy test at screening for women of childbearing potential.
• Subjects must use highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1% per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.)

You may not qualify if…

• Patients with prior allogeneic stem cell transplantation (SCT) who have had:
• allo-SCT performed <3 months prior to enrollment; or
• immunosuppressive treatment for acute or chronic graft-versus-host disease (GVHD) within 3 months prior to enrollment (with the exception of those patients who required ≤15 mg/day oral prednisone or equivalent); or
• acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified Seattle Glucksberg Criteria); or
• prior chronic GVHD (as defined by the NIH Consensus Development Project), persisting for >6 months, which required systemic immunosuppression (with the exception of those patients who required ≤15 mg/day oral prednisone or equivalent); or
• a donor lymphocyte infusion (DLI) within 6 months prior to enrollment; or
• is currently on treatment with GVHD prophylaxis medications tacrolimus, sirolimus, or cyclosporine
• Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are acceptable.
• Known severe hypersensitivity reactions to Azacitidine or to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia, vitiligo, and sensory neuropathy Grade ≤ 2 is acceptable
• a. Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with Avelumab and/or Azacitidine (e.g., hearing loss) may be included after consultation with the Study Physician.
• Pregnancy or lactation
• Known alcohol or drug abuse
• All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject"s tolerance of trial treatment
• Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject"s ability to sign informed consent, cooperate, or participate in the study.
• Vaccination within 4 weeks of the first dose of Azacitidine and while on trial is prohibited except for administration of inactivated vaccines
• History of idiopathic pulmonary fibrosis, organizing pneumonitis (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis

Where it is running

• Memorial Sloan Kettering Cancer Center — New York, New York, United States

Full record on ClinicalTrials.gov

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